Podcasts about sglt

It's In the News.. a look at the top headlines and stories in the diabetes community. This week's top stories: Dexcom updates investors on its 15-day sensor, TrialNet marks a big anniversary, Beta Bionics goes public, NFL fans support Mark Andrews and much more! Find out more about Moms' Night Out  Please visit our Sponsors & Partners - they help make the show possible! Learn more about Gvoke Glucagon Gvoke HypoPen® (glucagon injection): Glucagon Injection For Very Low Blood Sugar (gvokeglucagon.com) Omnipod - Simplify Life Learn about Dexcom  Edgepark Medical Supplies Check out VIVI Cap to protect your insulin from extreme temperatures Learn more about AG1 from Athletic Greens  Drive research that matters through the T1D Exchange The best way to keep up with Stacey and the show is by signing up for our weekly newsletter: Sign up for our newsletter here Here's where to find us: Facebook (Group) Facebook (Page) Instagram Twitter Check out Stacey's books! Learn more about everything at our home page www.diabetes-connections.com  Reach out with questions or comments: info@diabetes-connections.com Episode transcription with links: Hello and welcome to Diabetes Connections In the News! I'm Stacey Simms and every other Friday I bring you a short episode with the top diabetes stories and headlines happening now. XX Couple of quick updates from the JP Morgan Healthcare Conference. Dexcom's CEO Kevin Sayer expects to launch a 15-day sensor in the second half of the year. That's in front of the FDA right now. Competitor Abbott currently has 15-day sensors with its Freestyle Libre 2 Plus and Freestyle Libre 3 Plus devices, which the FDA cleared in 2023. Sayer also talked about expanded insurance coverage for the G7, to include more people with type 2. They haven't pursued that with Stelo, the OTC version of their sensors. The company has begun work on a next-generation CGM. Sayer said the sensor will be smaller, less expensive and include better electronics. Dexcom is also studying new sensor probes, one of which can support multiple analytes, such as measuring lactate or ketones in addition to insulin.   https://www.medtechdive.com/news/dexcom-ceo-stelo-otc-strategy-jp-morgan/737424/ XX TrialNet reaches a big milestone – more than a quarter million people have learned their risk of developing T1D through screening. TrialNet screening is available to family members of those diagnosed with T1D. Having a family history of the disease places individuals at a 15 times greater risk than those with no family members with T1D. Over the course of VUMC's 18 years participating in the program, the community of T1D patients has become increasingly more engaged with research efforts. More than ever, there is an eagerness to give back to others by participating in clinical trials that could help revolutionize care for those diagnosed with or at risk of developing T1D. In such trials, TrialNet typically takes drugs already shown to be effective in treating other autoimmune diseases and seeks to determine their efficacy in treating, delaying or preventing T1D.   Spencer Mannahan, a 10-year-old patient at Monroe Carell Jr. Children's Hospital at Vanderbilt, is participating in a TrialNet study that is looking to determine whether a treatment regimen using both rituximab and abatacept can preserve insulin production in patients newly diagnosed with T1D. Russell, one of the PIs for the study (Protocol TN-25), also treated Spencer's father, Zach, when he was diagnosed with T1D as a child. She enrolled in a different TrialNet study (Protocol TN-31) examining the effect of abrocitinib and ritlecitinib on insulin production in newly diagnosed individuals. While the possibility exists that her insulin production could be preserved, O'Neal joined the study because it presented an opportunity to make a positive impact on future patients.     These clinical trials support TrialNet's goal of a future without T1D. Research is underway on new methods of blocking the advance of T1D in patients with diabetes-related antibodies. One study will investigate whether T cells that have been activated against insulin can be specifically targeted, rather than issuing a treatment that targets all the body's T cells (thus rendering the patient immunocompromised).   TrialNet, the largest clinical trial network assembled to change the course of Type 1 diabetes, is funded by the National Institutes of Health through grant number NCT00097292.   For more information about screening for Type 1 diabetes risk if it runs in your family, contact info@trialnet.org, visit www.trialnet.org, or contact the Vanderbilt Type 1 Diabetes TrialNet Program at 615-936-8638. https://news.vumc.org/2025/01/22/milestone-in-vumc-affiliated-diabetes-screening-and-research-program-underscores-impact-of-clinical-trials/   XX Another study links air pollution to type 2 diabetes. This is from Wayne State University, and established a robust association between exposure to benzene, a prevalent airborne volatile organic compound, and insulin resistance in humans across all ages. “In this study, we exposed mice to benzene to see how it affects their blood glucose levels and energy expenditure,” she explained. “Our research revealed that within seven days of exposure, they developed high blood glucose insulin levels.” https://today.wayne.edu/medicine/news/2025/01/23/study-links-air-pollution-exposure-to-type-2-diabetes-susceptibility-65321 XX Adults with overweight or obesity and type 2 diabetes who are given the sodium glucose cotransporter 2 (SGLT-2) inhibitor drug dapagliflozin alongside moderate calorie restriction achieve much higher rates of remission compared with calorie restriction alone. The researchers say this study provides a practical strategy to achieve remission for patients with early type 2 diabetes. As well as helping to lower blood sugar levels, SGLT-2 inhibitors can also lead to weight loss, but their effect alongside calorie restriction on diabetes remission has not yet been investigated in a randomised controlled trial.   To address this, researchers carried out a trial involving 328 patients with type 2 diabetes of less than six years' duration at 16 centres in mainland China from 12 June 2020 to 31 January 2023.   Participants were aged 20-70 years with a body mass index (BMI) greater than 25 and were not taking any anti-diabetic medication other than metformin. https://www.news-medical.net/news/20250123/Dapagliflozin-and-calorie-restriction-show-higher-remission-rates-in-type-2-diabetes.aspx XX Beta Bionics has set the terms for its plan to go public, with a goal of raising at least $114 million to support its artificial pancreas system for people with Type 1 diabetes. That's as we're recroding, it's likely they will have begun trading on the NASDAQ by now.. the ticker is BBNX. Beta Bionics' iLet system was first cleared by the FDA for people ages six and up with Type 1 diabetes in May 2023. The Fierce Medtech Fierce 15 winner has since expanded its blood sugar sensor compatibility to include Abbott's FreeStyle Libre and Dexcom's G6 and G7 platforms. The company also said it plans to pursue new clinical studies and an FDA clearance that would enable the iLet's use among people with Type 2 diabetes. The ultmite goal is to have a dual-chambered pump with both insulin and glucagon.. but I didn't find anything about that in the articles about this IPO.. I followed up with Beta Bionics and they told me that the dual chambered pump is still very much the goal. Not sure why most of the publications left that out.. but good to hear. https://www.fiercebiotech.com/medtech/artificial-pancreas-maker-beta-bionics-aims-raise-120m-nasdaq-ipo XX Large new study estimates the size of the current US population with type 1 diabetes and project growth over the next ten years. They say about 2 million live with type 1.. about 1.79 million adults and 290-thousand children. Growth in the ten years is predicted to be about 10% https://jheor.org/article/124604 XX The American Diabetes Association® (ADA) teams up with Xeris Pharmaceuticals® makers of Gvoke – ready to use emergency glucagon. It is estimated that up to 46% of people with type 1 diabetes and 21% of those with type 2 diabetes using insulin experience at least one severe hypoglycemia event each year.2 The ADA, with support from Xeris, seeks to rectify the low rates of appropriate glucagon prescriptions by developing education materials and training resources for health care professionals and people living with diabetes, as well as through a national awareness campaign to educate people on who is at risk for severe hypoglycemia and should have glucagon, preferably ready-to-use, as a safety net. https://www.prnewswire.com/news-releases/the-american-diabetes-association-and-xeris-pharmaceuticals-announce-national-collaboration-to-provide-life-saving-hypoglycemia-education-and-awareness-302355703.html XX XX Wearing a CGM makes pharmacy students better at counseling patients. New study randomly assigned students to wear a CGM during lab sessions.. those who did had a higher average counseling score during the encounter with a patient and a higher overall confidence score. There was also a statistically significant positive correlation between average confidence and average empathy, and empathy and counseling performance. https://www.drugtopics.com/view/hands-on-cgm-training-helps-student-pharmacists-prepare-for-career XX Mark Andrews Bills Mafia Baltimore Ravens tight end Mark Andrews received a host of negative attention after flubbing a potential game-tying two-point conversion in Sunday night's loss to the Buffalo Bills.   In the face of the online rage, Bills Mafia is again showing some support.   Bills fan Nicholas Howard kicked off a GoFundMe to back Breakthrough T1D, a global Type 1 diabetes research organization that Andrews has supported.   "As many of you know, Ravens TE wasn't able to catch the game-tying 2-point conversion and upset Ravens fans," Howard wrote. "On top of that, the TE has been receiving death threats and nasty comments after his performance last night. We want Bills Mafia to donate to Marks charity for [Type 1] diabetes."   As of Wednesday morning, the fund raised more than $50,000 for the charity.   Related Links Lamar Jackson, Ravens bemoan missed opportunities in loss to Bills, defend Mark Andrews Ravens WR Zay Flowers: Missing 2024 playoff run due to injury 'took a little toll on me' Biggest winners and losers from Sunday's Divisional Round NFL playoff games The Ravens thanked Bills fans for supporting Andrews.     "Shout out to Bills Mafia for showing support to our guy Mark Andrews and donating to the [BreakthroughT1D] organization, which works towards curing and improving the lives of those dealing with Type 1 diabetes," the club posted.   Andrews was diagnosed with Type 1 diabetes as a child, an autoimmune disease for which there is currently no cure. He's one of several NFL players diagnosed with Type 1 -- Kansas City Chiefs tight end Noah Gray is another.   "Breakthrough T1D [formerly JDRF] greatly appreciates the generosity of the Buffalo Bills community and the many fans who were compelled to donate after Sunday's game," the organization said in a statement to ESPN's Alaina Getzenberg. "These donations will support research and advocacy on behalf of the 1.6 million Americans who, like Mark Andrews, live with type 1 diabetes."   It's not the first time that Bills fans have donated to the cause of a non-Buffalo player. Back in January 2018, Buffalo fans famously donated to the charity of former Cincinnati Bengals quarterback Andy Dalton after his win over Baltimore helped Buffalo make its first playoff appearance in nearly two decades. Over and over again, Bills Mafia has shown it will support a good cause when some spew hate. https://www.nfl.com/news/bills-fans-supporting-ravens-te-mark-andrews-after-drop-by-donating-to-type-1-diabetes-research

Ads for Ozempic, Wegovy, and Zepbound are all over our televisions (at least here in the US). But are these injectables really the key to losing weight and keeping it off? In this episode, I'm digging into all of the science surrounding these popular weight-loss drugs, including - the differences between each of them - how they work (and don't work) - the unwanted side effects that come from using these medications - natural ways to increase your body's production of GLP-1 ... and more! --- Show Notes: References: Coursework from Master's in Human Nutrition & Functional Medicine Program at the University of Western States Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension Weight Loss Medications: GLP-1 Agonists and How They Work How Much Does Ozempic Cost? With & Without Insurance Zepbound vs. Ozempic: 5 Differences Between These Weekly Injections What Are Incretin Mimetics, and How Do They Affect Weight Loss, Blood Sugar, and Type 2 Diabetes? Strategies for minimizing muscle loss during use of incretin‐mimetic drugs for treatment of obesity The Positive Effects of Yerba Maté (Ilex paraguariensis) in Obesity Anti-obesity effects of Yerba Mate (Ilex Paraguariensis): a randomized, double-blind, placebo-controlled clinical trial The effect of psyllium on fasting blood sugar, HbA1c, HOMA IR, and insulin control: a GRADE-assessed systematic review and meta-analysis of randomized controlled trials Soluble fibers from psyllium improve glycemic response and body weight among diabetes type 2 patients (randomized control trial) Increased glucagon-like peptide-1 secretion may be involved in antidiabetic effects of ginsenosides Modulation of glucagon-like peptide-1 release by berberine: in vivo and in vitro studies The effects of berberine on inflammatory markers in Chinese patients with metabolic syndrome and related disorders: a meta‑analysis of randomized controlled trials Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins A High Dose of Dietary Berberine Improves Gut Wall Morphology, Despite an Expansion of Enterobacteriaceae and a Reduction in Beneficial Microbiota in Broiler Chickens Berberine enhances the AMPK activation and autophagy and mitigates high glucose-induced apoptosis of mouse podocytes Curcumin induces secretion of glucagon-like peptide-1 through an oxidation-dependent mechanism --- 135: What You Should Know Before Starting Ozempic Sign up for a 1:1 Discovery Call Join the Compass Method DIY Program Jump inside my Rock the Bloat Minicourse Get my Core-Gi Workout Program with the exclusive listener discount! Join my Brain Rewiring Masterclass You can learn more about me by following on IG @imperfectlypaigewellness or by checking out my blog, freebies, and offers on my website: https://imperfectlypaigewellness.com Please share with #PaigeTalksWellness to help get the word out about the show - and join the Imperfect Health Fam over on Facebook.

Type 2 diabetics can present with a DKA associated with SGLT-2 inhibitors.  And it may be euglycaemic.  So be wary.     Check out the Prescriber Update, Vol 45, No 4, Dec 2024 Check out the Stat Pearls page on DKA Lizzo JM, Goyal A, Gupta V. Adult Diabetic Ketoacidosis. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560723/    www.rnzcuc.org.nz podcast@rnzcuc.org.nz https://www.facebook.com/rnzcuc https://twitter.com/rnzcuc   Music licensed from www.premiumbeat.com Full Grip by Score Squad   This podcast is intended to assist in ongoing medical education and peer discussion for qualified health professionals.  Please ensure you work within your scope of practice at all times.  For personal medical advice always consult your usual doctor 

Sodium–glucose cotransporter (SGLT) 2 inhibitors are an exciting new class of drugs approved for the treatment of newly diagnosed diabetic cats. These drugs work by blocking the kidneys from reabsorbing glucose, which causes more glucose to be lost in urine and lowers blood glucose levels. Tune in to this episode of the VetFolio Voice podcast as host Dr. Cassi and her guest, Dr. Audrey Cook, explore when to consider an SGLT-2 inhibitor instead of insulin and how to successfully manage and monitor a cat receiving this treatment.

Join endocrine experts Vin Tangpricha, MD, PhD, FACE, Editor-in-Chief of Endocrine Practice (EP) and Professor of Medicine at Emory University School of Medicine, and Rifka C. Schulman-Rosenbaum, MD, FACE, FACP, Director of Inpatient Diabetes at Long Island Jewish Medical Center, Professor of Medicine at the Donald and Barbara Zucker School of Medicine at Northwell Health, and Chair Elect for the AACE 2025 Annual Meeting, as they discuss Dr. Schulman-Rosenbaum's EP article, “Sodium-Glucose Cotransporter 2 Inhibitors Should Be Avoided for the Inpatient Management of Hyperglycemia.” Tune in as they explore the complexities of managing inpatient hyperglycemia, the risks of SGLT-2 inhibitors in hospitalized patients, and who might be good candidates for safer alternatives like DPP-4 inhibitors and insulin. Packed with valuable insights and practical strategies, this discussion is essential for optimizing hospital-based diabetes care. Read the full article in the April 2024 issue of EP here.

Noninvasive cardiac testing (1:30), SGLT-2 inhibitors (5:30), opioid prescribing (8:10), children with hypertension (10:20), anemia in infants and children (12:00), premenstrual disorders (15:20), and holiday ICD-10 codes (18:00).

In their ongoing quest to improve diabetes management, researchers are searching for new insights into the mechanisms through which the body manages blood sugar levels. Prof. Eugenio Cersosimo and colleagues at the University of Texas Health Science Center recently reported a breakthrough that could change how we understand glucose control and increase our ability to manage type 2 diabetes. Their study examines two medications, dapagliflozin, an SGLT-2 inhibitor, and exenatide, a GLP-1 receptor agonist, and how they can work together to control blood sugar levels by exploiting a previously unknown kidney-to-liver signalling pathway. Their findings have unravelled some important underlying mechanisms that provide strong support for the cardio-renal protective effects reported in many large clinical trials with the use of SGLT-2 inhibitors in patients with type 2 diabetes. The demonstration that the kidney plays a central role in glucose regulation during exposure to SGLT-2 inhibitors represents a major advance in our understanding of diabetes treatment and the prevention of severe cardiovascular and renal complications.

Join Gary, Kate, Mark and Henry as they discuss text messages for adolescent vaping cessation, stopping BP meds in nursing home residents with dementia, the benefits of SGLT-2 inhibitors, and mobile phone app–based artificial intelligence for diagnosing melanoma. Click here for transcript, notes and links for this episode.

Vi är tillbaka och dricker te. Denna gång avslutar vi årets upplaga av Sveriges godaste lokala teblandning genom att presentera vinnaren. Det blir även prat om våra planer för nästa års tävling. Veckans te: Vinnaren i SGLT 2024Årets resultat:Tredje plats: Guteblandning, Prince PhilipAndra plats: Blackberry Maple, Brunkullans Svart Smaksatt TeVinnare: S:t Olav® - ett svart te för utflyktenLänkar: Thepodd - En podd om te - Hosted by Eva Fridh, Martin von Knorring106: Nadia från Teagramsweden | ProduktivitéetKontakt och credJingle skapad av Jim Jonsson på JTunes ProductionsLogo av Kjell Högvik HanssonJohan GustaphzonJohan Gustaphzon på InstagramMartin LindeskogMartin Lindeskog på TwitterMartin Lindeskog på InstagramProduktiviteetStöd oss på PatreonMaila ossProduktivitéet på FacebookProduktivitéet på InstagramProduktiviteet Podcast - YouTubeProduktivitéet.se – Produktiva tedrickareProduktivitéet - CaptivateLämna gärna ett omdöme på iTunesProduktivitéet är inspelat och redigerat i Ferrite Recording Studio på iOS.

Episode #175 In this Fasting Q&A episode, hosted by Coach Lisa Chance, Dr. Jason Fung answers questions from the TFM Community: Is sauerkraut OK for fat fasting or olives only? [03:10] What happens to the body weight set point when we are under stress? [04:11] I recently listened to a podcast from a few years ago where you and Dr. Peter Attia discussed insulin resistance. You said you had evolved your thinking about it and that it was not like a lock and key that didn't fit, but, instead, more like an overflow situation. You described it as a suitcase (the cell) already filled to the point of overflowing with shirts (the glucose), and it just couldn't hold any more, you just couldn't stuff anymore in. You also said that it is hyperinsulinemia that drives metabolic syndrome, not insulin resistance. Is that your current view? [12:13]  Does an enema stimulate insulin? For example, a coffee enema with kefir, whey, or other added probiotics. [16:00]  When we exercise, our bodies will pump out blood glucose to help with the energy needed. For an insulin resistant person doing hard, aerobic exercise (such as HIIT or run/walk), does the raised blood glucose need insulin to process it? [17:31] When a person is doing regular exercise routines, do they need to replenish glycogen stores after a workout or does the body do this on its own? [19:22] I read an article recently about SGLT inhibitors which said they can stimulate autophagy. Is this true? [24:33] Protein requirements are so confusing. If a person has a lot of weight to lose and they have a lot of excess skin (which is protein you want the body to use to minimize all that loose skin when you are done losing weight), how do they know how much protein to eat? Would they need less protein the more weight they had to lose? Does eating less protein force the body to use the loose skin? Does eating too much or too little protein have consequences? [27:40] I have read some things that say 8 ounces of animal products per week is enough and more than that has negative effects (insulin resistance, elevated bad cholesterol, and other things), and so getting more protein from legumes, nuts, and seeds is a good idea. Also, the type of animal products makes a difference; it is not just the processing, but whether it is organic, pasture-raised, regenerative, etc. I think that it can be easy to interpret that, since saturated fat isn't as bad as we thought, we might eat more animal products or not-so-healthy animal products, and, while it might lower insulin and promote weight loss in the short term, there can be other long-term effects that are not so healthy. Can you comment? [34:19] LINKS The two podcast episodes Lisa mentioned were: GLP-1s Episode #163 - Fasting Q&A with Dr Jason Fung: Order of Fat Burning, Fasting With a Gastric Sleeve, BMR Fluctuation, GLP-1 Drugs, and More https://www.thefastingmethod.com/podcast/2024/7/30/fasting-q-a-with-dr-jason-fung-order-of-fat-burning-fasting-with-a-gastric-sleeve-bmr-fluctuation-glp-1-drugs-and-more Hair Loss Episode #163 - Fasting Q&A with Nadia Pateguana, ND: Children and Snacking, Food Intolerances Since Fasting, Meals to Break a Fast, Hair Loss, and More https://www.thefastingmethod.com/podcast/2023/3/28/-fasting-q-a-children-and-snacking-food-intolerances-since-fasting-meals-to-break-a-fast-hair-loss-and-more-   Please note that you need to be a member of the TFM Community to submit questions to the Q&A webinars with Dr. Fung but you can submit questions to our regular Q&A episodes here: https://bit.ly/TFMPodcastQs   Transcripts of all episodes are available at www.thefastingmethod.com on the Podcast page. Learn More About Our Community: https://www.thefastingmethod.com Join our FREE Facebook Group: https://bit.ly/TFMNetwork Watch Us On YouTube: https://bit.ly/TFMYouTube Follow Us on Instagram: @fastingmethod   This podcast is for educational purposes only and is not a substitute for professional care by a doctor or other qualified medical professional. You should always speak with your physician or other healthcare professional before doing any fasting, changing your diet, taking or adjusting  any medication or supplements, or adopting any treatment for a health problem. The use of any other products or services purchased by you as a result of this podcast does not create a healthcare provider-patient relationship between you and any of the experts affiliated with this podcast. Information and statements regarding dietary supplements have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease.

Ozempic is the latest weight-loss craze sweeping the world, and with good reason: it really is providing results. But is this "miracle" drug as miraculous as it seems to be? This is my 2nd most popular episode for a reason! In this episode, you'll learn: - what Ozempic and Wegovy actually do inside your body - the potential pros and cons of taking this peptide - why Ozempic isn't a magic weight-loss drug - alternative options to Ozempic to help you lose weight ... and more! Show Notes: Schedule a 1:1 Discovery Call with me! Coursework from Master's in Human Nutrition & Functional Medicine Program at the University of Western States Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis Link Between Ozempic and Gallbladder Disease? Ozempic Goes Way Off-Label Once-Weekly Semaglutide in Adults with Overweight or Obesity Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review What Is Ozempic and Why Is It Getting So Much Attention? Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension For Those With Eating Disorders, Ozempic Can Be A Triggering Nightmare Boosting GLP-1 by Natural Products GLP-1 Supplements Weight Loss Medications: GLP-1 Agonists and How They Work Get my Core-Gi Workout Program with the 15% off listener discount You can learn more about me by following on IG or Tiktok @imperfectlypaigewellness or by checking out my blog, freebies, and offers on my website: https://imperfectlypaigewellness.com Please share with #PaigeTalksWellness to help get the word out about the show - and join the Imperfect Health Fam over on Facebook.

Vi är tillbaka och dricker te, denna gång avslutar vi årets upplaga av Sveriges godaste lokala teblandning. Sist ut är Brunkullans svarta te från Brunkullans te i Östersund.Veckans te: BrunkullansBrunkullans Svart Smaksatt Te lösvikt – Brunkullans TeKontakt och credJingle skapad av Jim Jonsson på JTunes ProductionsLogo av Kjell Högvik HanssonJohan GustaphzonJohan Gustaphzon på InstagramMartin LindeskogMartin Lindeskog på TwitterMartin Lindeskog på InstagramProduktiviteetStöd oss på PatreonMaila ossProduktivitéet på FacebookProduktivitéet på InstagramProduktiviteet Podcast - YouTubeProduktivitéet.se – Produktiva tedrickareProduktivitéet - CaptivateLämna gärna ett omdöme på iTunesProduktivitéet är inspelat och redigerat i Ferrite Recording Studio på iOS.

CardioNerds Drs. Jason Feinman, Gurleen Kaur, and Rick Ferraro discuss the implementation of SGLT inhibitors in clinical practice with Dr. Alison Bailey. Notes were drafted by Dr. Jason Feinman. In this episode, we discuss the implementation of SGLTi in clinical practice scenarios, including for individuals with heart failure regardless of ejection fraction, those with chronic kidney disease, and those with diabetes mellitus. The group also discusses important side effects to monitor for, as well as how to counsel patients when prescribing these medications. This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - Clinical Implementation of SGLT Inhibitors For patients with heart failure with reduced ejection fraction, SGLT inhibitors reduce the composite outcome of cardiovascular death or heart failure hospitalization by 25%. SGLT inhibitors can be safely started in patients with an eGFR as low as 20. There are ongoing trials investigating the safety of these medications in individuals with eGFR lower than 20 or those who are receiving dialysis. An eGFR decrease of 3-5 ml/min on average is expected after starting an SGLTi, but this will stabilize over time and provides protective effects of renal dysfunction in the long run. Early data that suggested an association between SGLTi and bacterial UTI development hasn't panned out in the long run, but there is an association between SGLTi and the development of either genital mycotic infections or yeast infections. Perineal hygiene is important to prevent the development of either. A patient-centered, shared decision-making approach should guide the choice of agents for individuals with type 2 diabetes mellitus. In certain patients, it may be reasonable to choose an SGLTi as the first-line agent. Show notes - Clinical Implementation of SGLT Inhibitors What is the data supporting the use of SGLTi in HFpEF? The EMPEROR-Preserved and DELIVER trials investigated the impact of empagliflozin and dapagliflozin, respectively, on cardiovascular outcomes in patients with mildly reduced or preserved ejection fraction. The SOLOIST-WHF trial investigated a combined SGLT1/2 inhibitor, sotagliflozin, in patients with recently worsening heart failure, irrespective of ejection.SGLTi have been demonstrated to reduce the risk of cardiovascular death or worsening heart failure, including heart failure hospitalization, in these individuals. A meta-analysis of the EMPEROR-Preserved and DELIVER trials demonstrated a hazard ratio of 0.80 for cardiovascular death or first hospitalization for heart failure for empagliflozin or dapagliflozin over placebo in the setting of HFpEF. What is the data supporting the use of SGLTi in HFrEF? In addition to the SOLOIST-WHF trial that was previously discussed, the EMPEROR-HF and DAPA-HF investigated the impact of SGLTi medications in patients with HFrEF. In patients with HFrEF, SGLTi medications have been demonstrated to reduce the risk of either cardiovascular death or heart failure hospitalization. Dapagliflozin and empagliflozin had a pooled risk reduction of all-cause death of 13%, a pooled risk reduction of cardiovascular death of 14%, and a 26% reduction in the combination of CV death or first hospitalization for heart failure. What is the expected impact of SGLTi on renal function? Dapagliflozin, empagliflozin, sotagliflozin, ertugliflozin, and canagliflozin have all been studied for their impact on renal dysfunction in individuals both with and without diabetes. In the CANVAS trial,

Mrs. Martinez is a 64-year-old woman with 10 year-history of type 2 diabetes mellitus, HTN, and dyslipidemia. Her current medications include metformin, an SGLT-2 inhibitor, statin, ARB and thiazide diuretic. She is at EBP-advised goals including recent A1c=6.9%. Today, she reports she is feeling well. Her history and physical examination are unremarkable. She mentions that, for the past year, in addition to her prescribed medications, she drinks a special tea blend that her sister makes, taking this each day to help “draw out the sugar” in her blood. She states, “I feel much better when I take it.” Your most appropriate response is:A. “I don't believe the tea is helpful in controlling your blood sugar.”B. "Please stop using the tea until I can look into its contents."C. "Homemade teas might interact with your medicines”D. “Tell me more about how the tea draws out the sugar.”Visit fhea.com to learn more!

Vi är tillbaka och dricker te, återigen fortsätter vår tävling att utse Sveriges godaste lokala teblandning. Denna gång tävlar Guteblandning från Kränku i Visby. Veckans te: GuteblandningGuteblandning203: SGLT #1 | ProduktivitéetKontakt och credJingle skapad av Jim Jonsson på JTunes ProductionsLogo av Kjell Högvik HanssonJohan GustaphzonJohan Gustaphzon på InstagramMartin LindeskogMartin Lindeskog på TwitterMartin Lindeskog på InstagramProduktiviteetStöd oss på PatreonMaila ossProduktivitéet på FacebookProduktivitéet på InstagramProduktiviteet Podcast - YouTubeProduktivitéet.se – Produktiva tedrickareProduktivitéet - CaptivateLämna gärna ett omdöme på iTunesProduktivitéet är inspelat och redigerat i Ferrite Recording Studio på iOS.

Vi är tillbaka och dricker te, även denna vecka fortsätter vår tävling. Vi är på jakt efter Sveriges godaste lokala teblandning och denna gång tävlar Blackberry Maple från Tefrossa. Veckans te: Blackberry MapleTefrossas Blackberry Maple, svart teKontakt och credJingle skapad av Jim Jonsson på JTunes ProductionsLogo av Kjell Högvik HanssonJohan GustaphzonJohan Gustaphzon på InstagramMartin LindeskogMartin Lindeskog på TwitterMartin Lindeskog på InstagramProduktiviteetStöd oss på PatreonMaila ossProduktivitéet på FacebookProduktivitéet på InstagramProduktiviteet Podcast - YouTubeProduktivitéet.se – Produktiva tedrickareProduktivitéet - CaptivateLämna gärna ett omdöme på iTunesProduktivitéet är inspelat och redigerat i Ferrite Recording Studio på iOS.

In the September 24, 2024, JACC issue, Dr. Valentin Fuster presents the latest expert consensus on heart failure management, updating the 2019 guidelines with ten key changes. Highlights include a strong emphasis on SGLT inhibitors throughout hospitalization and a refined approach to managing heart failure patients, ensuring timely adjustments in therapy and improved patient care strategies.

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are one of the established treatments used to slow the progression of CKD and improve outcomes.  Could perhaps the glucagon-like peptide 1 (GLP-1) receptor agonists provide similar, additive, or different benefits in patients with CKD?  Guest Author: John Swegle, PharmD, BCPS, BCACP  Music by Good Talk

Vi är tillbaka och dricker te. Vi fortsätter vår tävling på jakt efter Sveriges godaste lokala teblandning. Denna gång är det S:t Olav från Tecentralen i Östersund som tävlar. Veckans te: S:t OlavS:t Olav® - ett svart te för utflyktenKontakt och credJingle skapad av Jim Jonsson på JTunes ProductionsLogo av Kjell Högvik HanssonJohan GustaphzonJohan Gustaphzon på InstagramMartin LindeskogMartin Lindeskog på TwitterMartin Lindeskog på InstagramProduktiviteetStöd oss på PatreonMaila ossProduktivitéet på FacebookProduktivitéet på InstagramProduktiviteet Podcast - YouTubeProduktivitéet.se – Produktiva tedrickareProduktivitéet - CaptivateLämna gärna ett omdöme på iTunesProduktivitéet är inspelat och redigerat i Ferrite Recording Studio på iOS.

Today's show is brought to you by MYOXCIENCE Nutrition. In this episode Matt Kaeberlein, PhD, CEO of Optispan, discusses the significance of enhancing health span through interventions like rapamycin and highlights the role of senescent cells in chronic inflammation and age-related diseases. Crush your workouts with the Creatine+ Electrolyte Combo by MYOXCIENCE: https://bit.ly/Electrolyte-Stix-Jar *Save with code podcast at checkout Link to show notes: https://bit.ly/4gdmxES Key Takeaways:  02:44 Pillars of health: eat, sleep, move, connect. 10:30 Eating protein and exercise can turn up mTOR. 15:20 High dietary protein and resistance training preserves muscle while aging. 19:20 Longevity research is underfunded. 25:10 Obesity was rare 50 years ago. 26:25 Fasting, and time restricting eating may not increase longevity. 30:45 Smoking, sedentary life, alcohol consumption and obesity shorten lifespan. 34:40 Resveratrol is not a longevity drug. 36:45 Spermidine is an autophagy booster. 38:10 Alpha ketoglutarate, urolithin A, and NAD precursors, may increase lifespan. 42:45 Acarbose, SGLT-2 inhibitors, and estrogens can increase lifespan. 44:45 Metformin does not corelate to reduced all-cause mortality. 47:30 NAD is a co-factor required for thousands of metabolic reactions. 52:55 Some epigenetic signatures are predictive of future health outcomes. 54:17 Facial imaging using AI can predict future health outcomes. 58:17 Dunedin Pace measures the rate of aging. 59:40 Optispan looks at epigenetics, blood glycan, and immune resilience/aging. 01:04:00 Senescent cells are cells that do not do their job and refuse to die. 01:07:50 Rapamycin impacts senescent cells, autoimmunity, and inflammation.    

Vi är tillbaka och dricker te. Äntligen börjat vår tävling att utse Sveriges godaste lokala teblandning. Först ut är Prince Philip från Indiska thé & kaffemagasinet i Göteborg. Veckans te: Prince PhilipPrince Philip - Indiska Thé & Kaffe MagasinetKontakt och credJingle skapad av Jim Jonsson på JTunes ProductionsLogo av Kjell Högvik HanssonJohan GustaphzonJohan Gustaphzon på InstagramMartin LindeskogMartin Lindeskog på TwitterMartin Lindeskog på InstagramProduktiviteetStöd oss på PatreonMaila ossProduktivitéet på FacebookProduktivitéet på InstagramProduktiviteet Podcast - YouTubeProduktivitéet.se – Produktiva tedrickareProduktivitéet - CaptivateLämna gärna ett omdöme på iTunesProduktivitéet är inspelat och redigerat i Ferrite Recording Studio på iOS.

Dr. Christoph Terkamp, Bereichsleiter Endokrinologie an der Medizinischen Hochschule Hannover, diskutiert mit Heiner Wedemeyer drei für den gastroenterologischen Alltag wichtige Punkte: Wie muss bei einer geplanten Endoskopie eine Steroidsubstitution bei Patienten mit Nebennierenrindeninsuffizienz erfolgen? Wann ist ein Pausieren von SGLT-2 Inhibitoren bei gastroenterologischen Patienten notwendig? Und kann eine Sedierung für eine Endoskopie bei Therapie mit Inkretinmimetika (GLP-1-Rezeptoragonisten) unproblematisch durchgeführt werden?

We're taking a short summer break, but we'll be back at the end of August with brand new episodes.  Lose your heart to NephMadness 2022! Dr. Joel Topf (@kidney_boy) and Dr. Sadiya Khan (@HeartDocSadiya) tackle the NephMadness 2022 Cardiorenal Syndrome region, leading us through the pathophysiology of cardiorenal syndrome, how to approach the creatinine “bump” with diuresis, managing patients with diuretic resistance, and more. Claim CME for this episode at curbsiders.vcuhealth.org! Episodes | Subscribe | Spotify | Swag! | Top Picks | Mailing List | thecurbsiders@gmail.com | Free CME! Show Segments Intro, disclaimer, guest bios Guest one-liners, Introduction to Nephmadness 2022 Case #1 from Kashlak: acute decompensated heart failure with elevated creatinine Definition and pathophysiology of cardiorenal syndrome Use of home ACE-is/ARBs and SGLT-2 inhibitors in cardiorenal syndrome Case #2 from Kashlak: the creatinine bump with diuresis Approach to the creatinine bump with diuresis Tips for the volume exam Interpreting cardiac biomarkers in patients with chronic kidney disease Case #3 from Kashlak: diuretic resistance Maximizing loop diuretic efficacy Sequential nephron blockade Use of hypertonic saline Outro Credits Producer, Writer, Show Notes, Infographics: Malini Gandhi Cover Art:  Beth Garbitelli Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP    Reviewer: Emi Okamoto MD, FACP Executive Producer: Beth Garbitelli Showrunner: Matthew Watto MD, FACP Editor: Clair Morgan of nodderly.com Guest: Dr. Joel Topf MD, Dr. Sadiya Khan MD Sponsor: Beginly Health Ready to take control of your job search? Visit beginlyhealth.com/curbsiders to get started.  Sponsor: Locumstory Tune in to The Locumstory Podcast on Spotify, Apple, or Google podcasts. Sponsor: Freed You can try Freed for free right now by going to freed.ai. And listeners of Curbsiders can use code CURB50 for $50 off their first month.

Pradeep is a brilliant geneticist and Director of Preventive Cardiology, holds the Paul & Phyllis Fireman Endowed Chair in Vascular Medicine at Mass General Hospital and on faculty at Harvard Medical School and the Broad Institute. His prolific research has been illuminating for the field of improving our approach to reduce the risk of heart disease. That's especially important because heart disease is the global (and US) #1 killer and is on the increase. We didn't get into lifestyle factors here since there was so much ground to cover on new tests. drugs, and strategies.A video snippet of our conversation on ApoB. Full videos of all Ground Truths podcasts can be seen on YouTube here. The audios are also available on Apple and Spotify.Transcript with links to key publications and audioEric Topol (00:06):Well, welcome to Ground Truths. I'm Eric Topol and with me is Pradeep Natarajan from Harvard. He's Director of Preventative Cardiology at the Mass General Brigham Health System and he has been lighting it up on the field of cardiovascular. We're going to get to lots of different parts of that story and so, Pradeep welcome.Pradeep Natarajan (00:31):Thanks Eric, really delighted and honored to be with you and have this discussion.Eric Topol (00:36):Well, for years I've been admiring your work and it's just accelerating and so there's so many things to get to. I thought maybe what we'd start off with is you recently wrote a New England Journal piece about two trials, two different drugs that could change the landscape of cardiovascular prevention in the future. I mean, that's one of the themes we're going to get to today is all these different markers and drugs that will change cardiology as we know it now. So maybe you could just give us a skinny on that New England Journal piece.Two New Lipid Targets With RNA DrugsPradeep Natarajan (01:16):Yeah, yeah, so these two agents, the trials were published at the same time. These phase two clinical trials for plozasiran, which is an siRNA against APOC3 and zodasiran, which is an siRNA against ANGPTL3. The reason why we have medicines against those targets are based on human genetics observations, that individuals with loss of function mutations and either of those genes have reduced lipids. For APOC3, it's reduced triglycerides for ANGPTL3 reduced LDL cholesterol and reduced triglycerides and also individuals that have those loss of function mutations also have lower risk for coronary artery disease. Now that's a very similar parallel to PCSK9. We have successful medicines that treat that target because people have found that carriers of loss of function mutations in PCSK9 lead to lower LDL cholesterol and lower coronary artery disease.(02:11):Now that suggests that therapeutic manipulation without significant side effects from the agents themselves for APOC3 and ANGPTL3 would be anticipated to also lower coronary artery disease risk potentially in complementary pathways to PCSK9. The interesting thing with those observations is that they all came from rare loss of function mutations that are enriched in populations of individuals. However, at least for PCSK9, has been demonstrated to have efficacy in large groups of individuals across different communities. So the theme of that piece was really just the need to study diverse populations because those insights are not always predictable about which communities are going to have those loss of function mutations and when you find them, they often have profound insights across much larger groups of individuals.Eric Topol (03:02):Well, there's a lot there that we can unpack a bit of it. One of them is the use of small interfering RNAs (siRNA) as drugs. We saw in the field of PCSK9, as you mentioned. First there were monoclonal antibodies directed against this target and then more recently, there's inclisiran which isn't an RNA play if you will, where you only have to take it twice a year and supposedly it's less expensive and I'm still having trouble in my practice getting patients covered on their insurance even though it's cheaper and much more convenient. But nonetheless, now we're seeing these RNA drugs and maybe you could comment about that part and then also the surprise that perhaps is unexplained is the glucose elevation.Pradeep Natarajan (03:53):Yeah, so for medicines and targets that have been discovered through human genetics, those I think are attractive for genetic-based therapies and longer interval dosing for the therapies, which is what siRNAs allow you to do because the individuals that have these perturbations, basically the naturally occurring loss of function mutations, they have these lifelong, so basically have had a one-time therapy and have lived, and so far, at least for these targets, have not had untoward side effects or untoward phenotypic consequences and only reduce lipids and reduce coronary artery disease. And so, instead of taking a pill daily, if we have conviction that that long amount of suppression may be beneficial, then longer interval dosing and not worrying about the pill burden is very attractive specifically for those specific therapeutics. And as you know, people continue to innovate on further prolonging as it relates to PCSK9.(04:57):Separately, some folks are also developing pills because many people do feel that there's still a market and comfort for daily pills. Now interestingly for the siRNA for zodasiran at the highest dose, actually for both of them at the highest doses, but particularly for zodasiran, there was an increase in insulin resistance parameters actually as it relates to hyperglycemia and less so as it relates to insulin resistance, that is not predicted based on the human genetics. Individuals with loss of function mutations do not have increased risks in hyperglycemia or type 2 diabetes, so that isolates it related to that specific platform or that specific technology. Now inclisiran, as you'd mentioned, Eric is out there. That's an siRNA against PCSK9 that's made by a different manufacturer. So far, the clinical trials have not shown hyperglycemia or type 2 diabetes as it relates inclisiran, so it may be related to the specific siRNAs that are used for those targets. That does merit further consideration. Now, the doses that the manufacturers do plan to use in the phase three clinical trials are at lower doses where there was not an increase in hyperglycemia, but that does merit further investigation to really understand why that's the case. Is that an expected generalized effect for siRNAs? Is it related to siRNAs for this specific target or is it just related to the platform used for these two agents which are made by the same manufacturer?Eric Topol (06:27):Right, and I think the fact that it's a mystery is intriguing at the least, and it may not come up at the doses that are used in the trials, but the fact that it did crop up at high doses is unexpected. Now that is part of a much bigger story is that up until now our armamentarium has been statins and ezetimibe to treat lipids, but it's rapidly expanding Lp(a), which for decades as a cardiologist we had nothing to offer. There may even be drugs to be able to lower people who are at high risk with high Lp(a). Maybe you could discuss that.What About Lp(a)?Pradeep Natarajan (07:13):Yeah, I mean, Eric, as you know, Lp(a) has been described as a cardiovascular disease risk factors for quite so many years and there are assays to detect lipoprotein(a) elevation and have been in widespread clinical practice increasing widespread clinical practice, but we don't yet have approved therapies. However, there is an abundance of literature preclinical data that suggests that it likely is a causal factor, meaning that if you lower lipoprotein(a) when elevated, you would reduce the risk related to lipoprotein(a). And a lot of this comes from similar human genetic studies. The major challenge of just relating a biomarker to an outcome is there are many different reasons why a biomarker might be elevated, and so if you detect a signal that correlates a biomarker, a concentration to a clinical outcome, it could be related to that biomarker, but it could be to the other reasons that the biomarker is elevated and sometimes it relates to the outcome itself.(08:10):Now human genetics is very attractive because if you find alleles that strongly relate to that exposure, you can test those alleles themselves with the clinical outcome. Now the allele assignment is established at birth. No other factor is going to change that assignment after conception, and so that provides a robust, strong causal test for that potential exposure in clinical outcome. Now, lipoprotein(a) is unique in that it is highly heritable and so there are lots of different alleles that relate to lipoprotein(a) and so in a well powered analysis can actually test the lipoprotein(a) SNPs with the clinical outcomes and similar to how there is a biomarker association with incident myocardial infarction and incident stroke, the SNPs related to lipoprotein(a) show the same. That is among the evidence that strongly supports that this might be causal. Now, fast forward to many years later, we have at least three phase three randomized clinical trials testing agents that have been shown to be very potent at lowering lipoprotein(a) that in the coming years we will know if that hypothesis is true. Importantly, we will have to understand what are the potential side effects of these medicines. There are antisense oligonucleotides and siRNAs that are primarily in investigation. Again, this is an example where there's a strong genetic observation, and so these genetic based longer interval dosing therapies may be attractive, but side effects will be a key thing as well too. Those things hard to anticipate really can anticipate based on the human genetics for off target effects, for example.(09:52):It's clearly a risk signal and hopefully in the near future we're going to have specific therapies.Eric Topol (09:57):Yeah, you did a great job of explaining Mendelian randomization and the fact the power of genetics, which we're going to get into deeper shortly, but the other point is that do you expect now that there's these multiple drugs that lower Lp(a) efficiently, would that be enough to get approval or will it have to be trials to demonstrate improved cardiovascular outcomes?Pradeep Natarajan (10:24):There is a great regulatory path at FDA for approval just for LDL cholesterol lowering and inclisiran is on the market and the phase three outcomes data has not yet been reported because there is a wide appreciation that LDL cholesterol lowering is a pretty good surrogate for cardiovascular disease risk lowering. The label will be restricted to LDL cholesterol lowering and then if demonstrated to have clinical outcomes, the label could be expanded. For other biomarkers including lipoprotein(a), even though we have strong conviction that it is likely a causal factor there hasn't met the bar yet to get approval just based on lipoprotein(a) lowering, and so we would need to see the outcomes effects and then we would also need to understand side effects. There is a body of literature of side effects for other therapies that have targeted using antisense oligonucleotides. We talked about potential side effects from some siRNA platforms and sometimes those effects could overtake potential benefits, so that really needs to be assessed and there is a literature and other examples.(11:31):The other thing I do want to note related to lipoprotein(a) is that the human genetics are modeled based on lifelong perturbations, really hard to understand what the effects are, how great of an effect there might be in different contexts, particularly when introduced in middle age. There's a lot of discussion about how high lipoprotein(a) should be to deliver these therapies because the conventional teaching is that one in five individuals has high lipoprotein(a), and that's basically greater than 75 nanomoles per liter. However, some studies some human genetic studies to say if you want to get an effect that is similar to the LDL cholesterol lowering medicines on the market, you need to start with actually higher lipoprotein(a) because you need larger amounts of lipoprotein(a) lowering. Those are studies and approaches that haven't been well validated. We don't know if that's a valid approach because that's modeling based on this sort of lifelong effect. So I'm very curious to see what the overall effect will be because to get approval, I think you need to demonstrate safety and efficacy, but most importantly, these manufacturers and we as clinicians are trying to find viable therapies in the market that it won't be hard for us to get approval because hopefully the clinical trial will have said this is the context where it works. It works really well and it works really well on top of the existing therapies, so there are multiple hurdles to actually getting it directly to our patients.How Low Do You Go with LDL Cholesterol?Eric Topol (13:02):Yeah, no question about that. I'm glad you've emphasized that. Just as you've emphasized the incredible lessons from the genetics of people that have helped guide this renaissance to better drugs to prevent cardiovascular disease. LDL, which is perhaps the most impressive surrogate in medicine, a lab test that you already touched on, one of the biggest questions is how low do you go? That is Eugene Braunwald, who we all know and love. They're in Boston. The last time I got together with him, he was getting his LDL down to close to zero with various tactics that might be extreme. But before we leave these markers, you're running preventive cardiology at man's greatest hospital. Could you tell us what is your recipe for how aggressive do you go with LDL?Pradeep Natarajan (14:04):Yeah, so when I talk to patients where we're newly getting lipid lowering therapies on, especially because many people don't have a readout of abnormal LDL cholesterol when we're prescribing these medicines, it's just giving them a sense of what we think an optimal LDL cholesterol might be. And a lot of this is based on just empirical observations. So one, the average LDL cholesterol in the modern human is about 100 to 110 mg/dL. However, if you look at contemporary hunter gatherers and non-human primates, their average LDL is about 40 to 50 and newborn babies have an LDL cholesterol of about 30. And the reason why people keep making LDL cholesterol lowering medicines because as you stack on therapies, cardiovascular disease events continue to reduce including down to these very low LDL cholesterol values. So the population mean for LDL cholesterol is high and everybody likely has hypercholesterolemia, and that's because over the last 10,000 years how we live our lives is so dramatically different and there has not been substantial evolution over that time to change many of these features related to metabolism.(15:16):And so, to achieve those really low LDL cholesterol values in today's society is almost impossible without pharmacotherapies. You could say, okay, maybe everybody should be on pharmacotherapies, and I think if you did that, you probably would reduce a lot of events. You'll also be treating a lot of individuals who likely would not get events. Cardiovascular disease is the leading killer, but there are many things that people suffer from and most of the times it still is not cardiovascular disease. So our practice is still rooted in better identifying the individuals who are at risk for cardiovascular disease. And so, far we target our therapies primarily in those who have already developed cardiovascular disease. Maybe we'll talk about better identifying those at risk, but for those individuals it makes lots of sense to get it as low as possible. And the field has continued to move to lower targets.(16:07):One, because we've all recognized, at least based on these empirical observations that lower is better. But now increasingly we have a lot of therapies to actually get there, and my hope is that with more and more options and the market forces that influence that the cost perspective will make sense as we continue to develop more. As an aside, related aside is if you look at the last cholesterol guidelines, this is 2018 in the US this is the first time PCSK9 inhibitors were introduced in the guidelines and all throughout that there was discussions of cost. There are a lot of concerns from the field that PCSK9 inhibitors would bankrupt the system because so many people were on statins. And you look at the prior one that was in 2013 and cost was mentioned once it's just the cost effectiveness of statins. So I think the field has that overall concern.(17:01):However, over time we've gotten comfortable with lower targets, there are more medicines and I think some of this competition hopefully will drive down some of the costs, but also the overall appreciation of the science related to LDL. So long-winded way of saying this is kind of the things that we discussed just to give reassurance that we can go to low LDL cholesterol values and that it's safe and then we think also very effective. Nobody knows what the lower limit is, whether zero is appropriate or not. We know that glucose can get too low. We know that blood pressure can be too low. We don't know yet that limit for LDL cholesterol. I mean increasingly with these trials we'll see it going down really low and then we'll better appreciate and understand, so we'll see 40 is probably the right range.Eric Topol (17:49):40, you said? Yeah, okay, I'll buy that. Of course, the other thing that we do know is that if you push to the highest dose statins to get there, you might in some people start to see the hyperglycemia issue, which is still not fully understood and whether that is, I mean it's not desirable, but whether or not it is an issue, I guess it's still out there dangling. Now the other thing that since we're on LDL, we covered Lp(a), PCSK9, the siRNA, is ApoB. Do you measure ApoB in all your patients? Should that be the norm?Measuring ApoBPradeep Natarajan (18:32):Yeah, so ApoB is another blood test. In the standard lipid panel, you get four things. What's measured is cholesterol and triglycerides, they're the lipids insoluble in blood to get to the different tissues that get packaged in lipoprotein molecules which will have the cholesterol, triglycerides and some other lipids and proteins. And so, they all have different names as you know, right? Low density lipoprotein, high density lipoprotein and some others. But also in the lipid panel you get the HDL cholesterol, the amount of cholesterol in an HDL particle, and then most labs will calculate LDL cholesterol and LDL cholesterol has a nice relationship with cardiovascular disease. You lower it with statins and others. Lower risk for cardiovascular disease, turns out a unifying feature of all of these atherogenic lipoproteins, all these lipoproteins that are measured and unmeasured that relate to cardiovascular disease, including lipoprotein(a), they all have an additional protein called ApoB. And ApoB, at least as it relates to LDL is a pretty good surrogate of the number of LDL particles.(19:37):Turns out that that is a bit better at the population level at predicting cardiovascular disease beyond LDL cholesterol itself. And where it can be particularly helpful is that there are some patients out there that have an unexpected ratio between ApoB and LDL. In general, the ratio between LDL cholesterol and ApoB is about 1.1 and most people will have that rough ratio. I verify that that is the expected, and then if that is the expected, then really there is no role to follow ApoB. However, primarily the patients that have features related to insulin resistance have obesity. They may often have adequate looking LDL cholesterols, but their ApoB is higher. They have more circulating LDL particles relative to the total amount of LDL cholesterol, so smaller particles themselves. However, the total number of particles may actually be too high for them.(20:34):And so, even if the LDL cholesterol is at target, if the ApoB is higher, then you need to reduce. So usually the times that I just kind of verify that I'm at appropriate target is I check the LDL cholesterol, if that looks good, verify with the ApoB because of this ratio, the ApoB target should be about 10% lower. So if we're aiming for about 40, that's like 36, so relatively similar, and if it's there, I'm good. If it's not and it's higher, then obviously increase the LDL cholesterol lowering medicines because lower the ApoB and then follow the ApoB with the lipids going forward. The European Society of Cardiology has more emphasis on measuring ApoB, that is not as strong in the US guidelines, but there are many folks in the field, preventive cardiologists and others that are advocating for the increasing use of ApoB because I think there are many folks that are not getting to the appropriate targets because we are not measuring ApoB.Why Aren't We Measuring and Treating Inflammation?Eric Topol (21:37):Yeah, I think you reviewed it so well. The problem here is it could be part of the standard lipid panel, it would make this easy, but what you've done is a prudent way of selecting out people who it becomes more important to measure and moderate subsequently. Now this gets us to the fact that we're lipid centric and we don't pay homage to inflammation. So I wrote a recent Substack on the big miss on inflammation, and here you get into things like the monoclonal antibody to interleukin-6, the trial that CANTOS that showed significant reduction in cardiovascular events and fatal cancers by the way. And then you get into these colchicine trials two pretty good size randomized trials, and here the entry was coronary disease with a high C-reactive protein. Now somehow or other we abandon measuring CRP or other inflammatory markers, and both of us have had patients who have low LDLs but have heart attacks or significant coronary disease. So why don't we embrace inflammation? Why don't we measure it? Why don't we have better markers? Why is this just sitting there where we could do so much better? Even agents that are basically cost pennies like colchicine at low doses, not having to use a proprietary version could be helpful. What are your thoughts about us upgrading our prevention with inflammation markers?Pradeep Natarajan (23:22):Yeah, I mean, Eric, there is an urgent need to address these other pathways. I say urgent need because heart disease has the dubious distinction of being the leading killer in the US and then over the last 20 years, the leading killer in the world as it takes over non-communicable diseases. And really since the early 1900s, there has been a focus on developing pharmacotherapies and approaches to address the traditional modifiable cardiovascular disease risk factors. That has done tremendous good, but still the curves are largely flattening out. But in the US and in many parts of the world, the deaths attributable to cardiovascular disease are starting to tick up, and that means there are many additional pathways, many of them that we have well recognized including inflammation. More recently, Lp(a) that are likely important for cardiovascular disease, for inflammation, as you have highlighted, has been validated in randomized controlled trials.(24:18):Really the key trial that has been more most specific is one on Canakinumab in the CANTOS trial IL-1β monoclonal antibody secondary prevention, so cardiovascular disease plus high C-reactive protein, about a 15% reduction in cardiovascular disease and also improvement in cancer related outcomes. Major issues, a couple of issues. One was increased risk for severe infections, and the other one is almost pragmatic or practical is that that medicine was on the market at a very high price point for rare autoinflammatory conditions. It still is. And so, to have for a broader indication like cardiovascular disease prevention would not make sense at that price point. And the manufacturer tried to go to the FDA and focus on the group that only had C-reactive protein lowering, but that's obviously like a backwards endpoint. How would you know that before you release the medicine? So that never made it to a broader indication.(25:14):However, that stuck a flag in the broader validation of that specific pathway in cardiovascular disease. That pathway has direct relevance to C-reactive protein. C-reactive protein is kind of a readout of that pathway that starts from the NLRP3 inflammasome, which then activates IL-1β and IL-6. C-reactive protein we think is just a non causal readout, but is a reliable test of many of these features and that's debatable. There may be other things like measuring IL-6, for example. So given that there is actually substantial ongoing drug development in that pathway, there are a handful of companies with NLRP3 inflammasome inhibitors, but small molecules that you can take as pills. There is a monoclonal antibody against IL-6 that's in development ziltivekimab that's directed at patients with chronic kidney disease who have lots of cardiovascular disease events despite addressing modifiable risk factors where inflammatory markers are through the roof.(26:16):But then you would also highlighted one anti-inflammatory that's out there that's pennies on the dollar, that's colchicine. Colchicine is believed to influence cardiovascular disease by inhibiting NLRP3, I say believed to. It does a lot of things. It is an old medicine, but empirically has been shown in at least two randomized controlled trials patients with coronary artery disease, actually they didn't measure C-reactive protein in the inclusion for these, but in those populations we did reduce major adverse cardiovascular disease events. The one thing that does give me pause with colchicine is that there is this odd signal for increased non-cardiovascular death. Nobody understands if that's real, if that's a fluke. The FDA just approved last year low dose colchicine, colchicine at 0.5 milligrams for secondary prevention given the overwhelming efficacy. Hasn't yet made it into prevention guidelines, but I think that's one part that does give me a little bit pause. I do really think about it particularly for patients who have had recurrent events. The people who market the medicine and do research do remind us that C-reactive protein was not required in the inclusion, but nobody has done that secondary assessment to see if measuring C-reactive protein would be helpful in identifying the beneficial patients. But I think there still could be more work done on better identifying who would benefit from colchicine because it's an available and cheap medicine. But I'm excited that there is a lot of development in this inflammation area.Eric Topol (27:48):Yeah, well, the development sounds great. It's probably some years away. Do you use colchicine in your practice?Pradeep Natarajan (27:56):I do. Again, for those folks who have had recurrent events, even though C-reactive protein isn't there, it does make me feel like I'm treating inflammation. If C-reactive protein is elevated and then I use it for those patients, if it's not elevated, it's a much harder sell from my standpoint, from the patient standpoint. At the lower dose for colchicine, people generally are okay as far as side effects. The manufacturer has it at 0.5 milligrams, which is technically not pennies on the dollar. That's not generic. The 0.6 milligrams is generic and they claim that there is less side effects at the 0.5 milligrams. So technically 0.6 milligrams is off label. So it is what it is.CHIP and Defining High Risk People for CV DiseaseEric Topol (28:40):It's a lot more practical, that's for sure. Now, before I leave that, I just want to mention when I reviewed the IL-1β trial, you mentioned the CANTOS trial and also the colchicine data. The numbers of absolute increases for infection with the antibody or the cancers with the colchicine are really small. So I mean the benefit was overriding, but I certainly agree with your concern that there's some things we don't understand there that need to be probed more. Now, one of the other themes, well before one other marker that before we get to polygenic risk scores, which is center stage here, defining high risk people. We've talked a lot about the conventional things and some of the newer ways, but you've been one of the leaders of study of clonal hematopoiesis of indeterminate potential known as CHIP. CHIP, not the chips set in your computer, but CHIP. And basically this is stem cell mutations that increase in people as we age and become exceptionally common with different mutations that account in these clones. So maybe you can tell us about CHIP and what I don't understand is that it has tremendous correlation association with cardiovascular outcomes adverse as well as other system outcomes, and we don't measure it and we could measure it. So please take us through what the hell is wrong there.Pradeep Natarajan (30:14):Yeah, I mean this is really exciting. I mean I'm a little bit biased, but this is observations that have been made only really over the last decade, but accelerating research. And this has been enabled by advances in genomic technologies. So about 10 years or plus ago, really getting into the early days of population-based next generation sequencing, primarily whole exome sequencing. And most of the DNA that we collect to do these population-based analyses come from the blood, red blood cells are anucleate, so they're coming from white blood cells. And so, at that time, primarily interrogating what is the germline genetic basis for coronary artery disease and early onset myocardial infarction. At the same time, colleagues at the Broad Institute were noticing that there are many additional features that you can get from the blood-based DNA that was being processed by the whole exome data. And there were actually three different groups that converged on that all in Boston that converged on the same observation that many well-established cancer causing mutations.(31:19):So mutations that are observed in cancers that have been described to drive the cancers themselves were being observed in these large population-based data sets that we were all generating to understand the relationship between loss of function mutations in cardiovascular disease. That's basically the intention of those data sets for being generated for other things. Strong correlation with age, but it was very common among individuals greater than 70; 10% of them would have these mutations and is very common because blood cancer is extremely, it's still pretty rare in the population. So to say 10% of people had cancer causing driver mutations but didn't have cancer, was much higher than anyone would've otherwise expected. In 2014, there were basically three main papers that described that, and they also observed that there is a greater risk of death. You'd say, okay, this is a precancerous lesion, so they're probably dying of cancer.(32:17):But as I said, the absolute incidence rate for blood cancer is really low and there's a relative increase for about tenfold, but pretty small as it relates to what could be related to death. And in one of the studies we did some exploratory analysis that suggested maybe it's actually the most common cause of death and that was cardiovascular disease. And so, a few years later we published a study that really in depth really looked at a bunch of different data sets that were ascertained to really understand the relationship between these mutations, these cancer causing mutations in cardiovascular disease, so observed it in enrichment and older individuals that had these mutations, CHIP mutations, younger individuals who had early onset MI as well too, and then also look prospectively and showed that it related to incident coronary artery disease. Now the major challenge for this kind of analysis as it relates to the germline genetic analysis is prevalence changes over time.(33:15):There are many things that could influence the presence of clonal hematopoiesis. Age is a key enriching factor and age is the best predictor for cardiovascular disease. So really important. So then we modeled it in mice. It was actually a parallel effort at Boston University (BU) that was doing the same thing really based on the 2014 studies. And so, at the same time we also observed when you modeled this in mice, you basically perturb introduce loss of function mutations in the bone marrow for these mice to recapitulate these driver mutations and those mice also have a greater burden of atherosclerosis. And Eric, you highlighted inflammation because basically the phenotype of these cells are hyper inflamed cells. Interestingly, C-reactive protein is only modestly elevated. So C-reactive protein is not fully capturing this, but many of the cytokines IL-1β, IL-6, they're all upregulated in mice and in humans when measured as well.(34:11):Now there've been a few key studies that have been really exciting about using anti-inflammatories in this pathway to address CHIP associated cardiovascular disease. So one that effort that I said in BU because they saw these cytokines increased, we already know that these cytokines have relationship with atherosclerosis. So they gave an NLRP3 inflammasome inhibitor to the mice and they showed that the mice with or without CHIP had a reduction in atherosclerosis, but there was a substantial delta among the mice that are modeled as having CHIP. Now, the investigators in CANTOS, the manufacturers, they actually went back and they survey where they had DNA in the CANTOS trial. They measured CHIP and particularly TET2 CHIP, which is the one that has the strongest signal for atherosclerosis. As I said, overall about 15% reduction in the primary outcome in CANTOS. Among the individuals who had TET2 CHIP, it was a 64% reduction in event.(35:08):I mean you don't see those in atherosclerosis related trials. Now this has the caveat of it being secondary post hoc exploratory, the two levels of evidence. And so, then we took a Mendelian randomization approach. Serendipitously, just so happens there is a coding mutation in the IL-6 receptor, a missense mutation that in 2012 was described that if you had this mutation, about 40% of people have it, you have a 5%, but statistically significant reduction in coronary artery disease. So we very simply said, if the pathway of this NLRP3 inflammasome, which includes IL-6, if you have decreased signaling in that pathway, might you have an even greater benefit from having that mutation if you had CHIP versus those who didn't have CHIP. So we looked in the UK Biobank, those who didn't have CHIP 5% reduction, who had that IL-6 receptor mutation, and then those who did have CHIP, if they had that mutation, it was about a 60% reduction in cardiovascular disease.(36:12):Again, three different lines of evidence that really show that this pathway has relevance in the general population, but the people who actually might benefit the most are those with CHIP. And I think as we get more and more data sets, we find that not all of the CHIP mutations are the same as it relates to cardiovascular disease risk. It does hone in on these key subsets like TET2 and JAK2, but this is pretty cool as a preventive cardiologist, new potential modifiable risk factor, but now it's almost like an oncologic paradigm that is being applied to coronary artery disease where we have specific driver mutations and then we're tailoring our therapies to those specific biological drivers for coronary artery disease. Hopefully, I did that justice. There's a lot there.Why Don't We Measure CHIP?Eric Topol (36:57):Well, actually, it's phenomenal how you've explained that, but I do want to review for our listeners or readers that prior to this point in our conversation, we were talking about germline mutations, the ones you're born with. With CHIP, we're talking about acquired somatic mutations, and these are our blood stem cells. And what is befuddling to me is that with all the data that you and others, you especially have been publishing and how easy it would be to measure this. I mean, we've seen that you can get it from sequencing no less other means. Why we don't measure this? I mean, why are we turning a blind eye to CHIP? I just don't get it. And we keep calling it of indeterminate potential, not indeterminate. It's definite potential.Pradeep Natarajan (37:51):Yeah, no, I think these are just overly cautious terms from the scientists. Lots of people have CHIP, a lot of people don't have clinical outcomes. And so, I think from the lens of a practicing hematologists that provide some reassurance on the spectrum for acquired mutation all the way over to leukemia, that is where it comes from. I don't love the acronym as well because every subfield in biomedicine has its own CHIP, so there's obviously lots of confusion there. CH or clinical hematopoiesis is often what I go, but I think continuing to be specific on these mutations. Now the question is why measure? Why aren't we measuring it? So there are some clinical assays out there. Now when patients get evaluated for cytopenias [low cell counts], there are next generation sequencing tests that look for these mutations in the process for evaluation. Now, technically by definition, CHIP means the presence of these driver mutations that have expanded because it's detectable by these assays, not a one-off cell because it can only be detected if it's in a number of cells.(38:55):So there has been some expansion, but there are no CBC abnormalities. Now, if there's a CBC abnormality and you see a CHIP mutation that's technically considered CCUS or clonal cytopenia of unknown significance, sometimes what is detected is myelodysplastic syndrome. In those scenarios still there is a cardiovascular disease signal, and so many of our patients who are seen in the cancer center who are being evaluated for these CBC abnormalities will be detected to have these mutations. They will have undergone some risk stratification to see what the malignancy potential is. Still pretty low for many of those individuals. And so, the major driver of health outcomes for this finding may be cardiovascular. So those patients then get referred to our program. Dana-Farber also has a similar program, and then my colleague Peter Libby at the Brigham often sees those patients as well. Now for prospective screening, so far, an insurance basically is who's going to pay for it.(39:51):So an insurance provider is not deemed that appropriate yet. You do need the prospective clinical trials because the medicines that we're talking about may have side effects as well too. And what is the yield? What is the diagnostic yield? Will there actually be a large effect estimate? But there has been more and more innovation, at least on the assay and the cost part of the assay because these initial studies, we've been using whole exome sequencing, which is continuing to come down, but is not a widely routine clinical test yet. And also because as you highlighted, these are acquired mutations. A single test is not necessarily one and done. This may be something that does require surveillance for particular high risk individuals. And we've described some risk factors for the prevalence of CHIP. So surveillance may be required, but because there are about 10 genes that are primarily implicated in CHIP, that can substantially decrease the cost of it. The cost for DNA extraction is going down, and so there are research tests that are kind of in the $10 to $20 range right now for CHIP. And if flipped over to the clinical side will also be reasonably low cost. And so, for the paradigm for clinical implementation, that cost part is necessary.Eric Topol (41:10):I don't know the $10 or $20 ones. Are there any I could order on patients that I'm worried about?Pradeep Natarajan (41:17):Not yet clinical. However, there is a company that makes the reagents for at least the cores that are developing this. They are commercializing that test so that many other cores, research cores can develop it. I think it's in short order that clinical labs will adopt it as well too.Eric Topol (41:36):That's great.Pradeep Natarajan (41:37):I will keep you apprised.What About Polygenic Risk Scores?Eric Topol (41:39):I think that's really good news because like I said, we're so darn lipid centric and we have to start to respect the body of data, the knowledge that you and others have built about CHIP. Now speaking of another one that drives me nuts is polygenic risk score (PRS) for about a decade, I've been saying we have coronary disease for most people is a polygenic trait. It's not just a familial hypercholesterolemia. And we progressively have gotten better and better of the hundreds of single variants that collectively without a parental history will be and independently predict who is at double, triple or whatever risk of getting heart disease, whereby you could then guide your statins at higher aggressive or pick a statin, use one or even go beyond that as we've been talking about. But we don't use that in practice, which is just incredible because it's can be done cheap.(42:45):You can get it through whether it's 23andMe or now many other entities. We have an app, MyGeneRank where we can process that Scripss does for free. And only recently, Mass General was the first to implement that in your patient population, and I'm sure you were a driver of that. What is the reluctance about using this as an orthogonal, if you will, separate way to assess a person's risk for heart disease? And we know validated very solidly about being aggressive about lipid lowering when you know this person's in the highest 5% polygenic risk score. Are we just deadheads in this field or what?Pradeep Natarajan (43:30):Yeah, I mean Eric, as you know, lots of inertia in medicine, but this one I think has a potential to make a large impact. Like CHIP mutations, I said news is about 10% in individuals greater than 70. The prospect here is to identify the risk much earlier in life because I think there is a very good argument that we're undertreating high risk individuals early on because we don't know how to identify them. As you highlighted, Dr. Braunwald about LDL cholesterol. The other part of that paradigm is LDL cholesterol lowering and the duration. And as we said, everybody would benefit from really low LDL cholesterol, but again, you might overtreat that if you just give that to everybody. But if you can better identify the folks very early in life, there is a low cost, low risk therapy, at least related to statins that you could have a profound benefit from the ones who have a greater conviction will have future risk for cardiovascular disease.(44:21):You highlighted the family history, and the family history has given the field of clues that genetics play a role. But as the genome-wide association studies have gotten larger, the polygenic risk scores have gotten better. We know that family history is imperfect. There are many reasons why a family member who is at risk may or may not have developed cardiovascular disease. A polygenic risk score will give a single number that will estimate the contribution of genetics to cardiovascular disease. And the thing that is really fascinating to me, which is I think some of a clinical implementation challenge is that the alleles for an individual are fixed. The genotyping is very cheap. That continues to be extremely cheap to do this test. But the weights and the interpretation of what the effects should be for each of the SNPs are continually being refined over time.(45:18):And so, given the exact same SNPs in the population, the ability to better predict cardiovascular diseases getting better. And so, you have things that get reported in the literature, but literally three years later that gets outdated and those hypotheses need to be reassessed. Today, I'll say we have a great relative to other things, but we have a great polygenic risk score was just reported last year that if you compare it to familial hypercholesterolemia, which has a diagnostic yield of about 1 in 300 individuals, but readily detectable by severe hypercholesterolemia that has about threefold risk for cardiovascular disease. By polygenic risk score, you can find 1 in 5 individuals with that same risk. Obviously you go higher than that, it'll be even higher risk related to that. And that is noble information very early in life. And most people develop risk factors later in life. It is happening earlier, but generally not in the 30s, 40s where there's an opportunity to make a substantial impact on the curve related to cardiovascular disease.(46:25):But there is a lot of momentum there. Lots of interest from NIH and others. The major challenge is though the US healthcare system is really not well set up to prevention, as you know, we practice healthcare after patient's developed disease and prevent the complications related to progression. The stakeholder incentives beyond the patient themselves are less well aligned. We've talked a lot here today about payers, but we don't have a single payer healthcare system. And patients at different times of their lives will have different insurers. They'll start early in life with their parents, their first employer, they'll move on to the next job and then ultimately Medicare. There's no entity beyond yourself that really cares about your longevity basically from the beginning and your overall wellness. That tension has been a major challenge in just driving the incentives and the push towards polygenic risk scores. But there are some innovative approaches like MassMutual Life Insurance actually did a pilot on polygenic risk scoring.(47:33):They're in the business of better understanding longevity. They get that this is important data. Major challenges, there are federal protections against non-discrimination in the workplace, health insurance, not necessarily life insurance. So I think that there are lots of things that have to be worked out. Everybody recognizes that this is important, but we really have to have all the incentives aligned for this to happen at a system-wide level in the US. So there's actually lots of investment in countries that have more nationalized healthcare systems, lots of development in clinical trials in the UK, for example. So it's possible that we in the US will not be the lead in that kind of evidence generation, but maybe we'll get there.The GLP-1 DrugsEric Topol (48:16):Yeah, it's frustrating though, Pradeep, because this has been incubating for some time and now we have multi ancestry, polygenic risk scores, particularly for heart disease and we're not using it, and it's not in my view, in the patient's best interest just because of these obstacles that you're mentioning, particularly here in the US. Well, the other thing I want to just get at with you today is the drugs that we were using for diabetes now blossoming for lots of other indications, particularly the glucagon-like peptide 1 (GLP-1) drugs. This has come onto the scene in recent years, not just obviously for obesity, but it's anti-inflammatory effects as we're learning, mediated not just through the brain but also T cells and having extraordinary impact in heart disease for people with obesity and also with those who have heart failure, about half of heart failure for preserved ejection fraction. So recently you and your colleagues recently published a paper with this signal of optic neuropathy. It was almost seven eightfold increase in a population. First, I wanted to get your sense about GLP-1. We're also going to get into the SGLT2 for a moment as well, but how do you use GLP-1? What's your prognosis for this drug class going forward?Pradeep Natarajan (49:55):As it relates to the paper, I can't claim credit as one of my former students who is now Mass Eye and Ear resident who participated, but we can talk about that. There's obviously some challenges for mining real world data, but this was related to anecdotes that they were observing at Mass Eye and Ear and then studied and observed an enrichment. In general though, I feel like every week I'm reading a new clinical trial about a new clinical outcome benefit as it relates to GLP-1 receptor agonists. This is kind of one thing that stands out that could be interrogated in these other clinical trials. So I would have that caveat before being cautious about ocular complications. But the data has been overwhelmingly beneficial, I think, because at minimum, obesity and inflammation are relayed to myriad of consequences, and I'm really excited that we have therapies that can address obesity that are safe.(50:52):There's a legacy of unsafe medicines for obesity, especially related to cardiovascular disease. So the fact that we have medicines that are safe and effective for lowering weight that also have real strong effects on clinical outcomes is tremendous. We in cardiology are increasingly using a range of diabetes medicines, including GLP-1 receptor agonists and SGLT2 inhibitors. I think that is also the secular changes of what influences cardiovascular disease over time. I talked about over the last 10 years or so with this increase in deaths attributable to cardiovascular disease. If you look at the influences of traditional clinical risk factors today, many of them have decreased in importance because when abnormal, we recognize them, in general we modify them when recognized. And so, many of the things that are unaddressed, especially the features related to insulin resistance, obesity, they start rising in importance. And so, there is a dramatic potential for these kinds of therapies in reducing the residual risks that we see related to cardiovascular disease. So I'm enthusiastic and excited. I think a lot more biology that needs to be understood of how much of this is being influenced specifically through this pathway versus a very effective weight loss medicine. But also interesting to see the insights on how the effect centrally on appetite suppression has profound influences on weight loss as well too. And hopefully that will lead to more innovations in weight management.The SGLT-2 DrugsEric Topol (52:25):And likewise, perhaps not getting near as much play, but when it came on the cardiovascular scene that an anti-diabetic drug SGLT2 was improving survival, that was big, and we still don't know why. I mean, there's some ideas that it might be a senolytic drug unknowingly, but this has become a big part of practice of cardiology in patients with diabetes or with preserved ejection fraction heart failure. Is that a fair summary for that drug?Pradeep Natarajan (53:00):Yeah, I totally agree. I mean, as there has been increased recognition for heart failure preserved ejection fraction, it has been almost disheartening over the last several years that we have not had very specific effective therapies to treat that condition. Now, it is a tremendous boon that we do have medicines interestingly focused on metabolism that are very helpful in that condition for heart failure with preserved ejection fraction. But there is still much more to be understood as far as that condition. I mean, the major challenge with heart failure, as you know, especially with heart failure preserved ejection fraction, it likely is a mix of a wide variety of different etiologies. So in parallel with developing effective therapies that get at some aspect is really understanding what are the individual drivers and then targeting those specific individual drivers. That requires a lot of unbiased discovery work and further profiling to be done. So lot more innovation, but relative to heart failure itself, it is not had widespread recognition as heart failure reduced ejection fraction. So much more to innovate on, for sure.Eric Topol (54:07):Right, right. Yeah, I am stunned by the recent progress in cardiovascular medicine. You have been center stage with a lot of it, and we've had a chance to review so much. And speaking of genetics, I wanted to just get a little insight because I recently came across the fact that your mother here at the City of Hope in Southern California is another famous researcher. And is that, I don't know what chromosome that is on regarding parental transmission of leading research. Maybe you can tell me about that.Pradeep Natarajan (54:41):Yeah, I mean, I guess it is a heritable trait when a parent has one profession that there is a higher likelihood that the offspring will have something similar. So both of my parents are PhDs, nonphysicians. There is a diabetes department at the City of Hope, so she's the chair of that department. So very active. We do overlap in some circles because she does investigate both vascular complications and renal complications. And then sometimes will ask my advice on some visualization. But she herself has just had a science translational medicine paper, for example, just a couple of months ago. So it's fun to talk about these things. To be honest, because my parents are researchers, I was not totally sure that I would be a researcher and kind of wanted to do something different in medicine. But many of my early observations and just how common cardiovascular disease is around me and in my community and wanting to do something useful is what got me specifically into cardiology.(55:45):But obviously there are numerous outstanding, important questions. And as I went through my career, really focused on more basic investigations of atherosclerosis and lipids. What got me excited sort of after my clinical training was the ability to ask many of these questions now in human populations with many new biological data sets, at least first centered on genetics. And the capabilities continue to expand, so now I teach first year Harvard medical students in their genetics curriculum. And when I talk to them just about my career arc, I do remind them they're all doing millions of things and they're exploring lots of things, but when they get to my shoes, the capabilities will be tremendously different. And so, I really advise them to take the different experiences, mainly in an exercise for asking questions, thoughtfully addressing questions, connecting it back to important clinical problems. And then once they start to understand that with a few different approaches, then they'll totally take off with what the opportunities are down the road.Eric Topol (56:51):No, it's great. I mean, how lucky somebody could be in the first year of med school with you as their teacher and model. Wow. Pradeep, we've really gone deep on this and it's been fun. I mean, if there's one person I'm going to talk to you about cardiovascular risk factors and the things that we've been into today, you would be the one. So thank you for taking the time and running through a lot of material here today, and all your work with great interest.Pradeep Natarajan (57:24):Thanks, Eric. I really appreciate it. It's tremendous honor. I'm a big fan, so I would be glad to talk about any of these things and more anytime.***************Thanks for listening, reading or watching!The Ground Truths newsletters and podcasts are all free, open-access, without ads.Please share this post/podcast with your friends and network if you found it informative!Voluntary paid subscriptions all go to support Scripps Research. 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CardioNerds Dr. Rick Ferraro, Dr. Gurleen Kaur, and Dr. Maryam Barkhordarian discuss the evidence and data supporting SGLT inhibition for cardiovascular and kidney health outcomes with expert faculty Dr. Muthu Vaduganathan. They discuss the role of SGLT inhibitors in different populations, including those with diabetes mellitus, heart failure, CKD, and myocardial infarction. Show notes and audio editing by CardioNerds Academy Fellow Dr. Maryam Barkhordarian. This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan The benefit of SGLT inhibition extends beyond diabetes, and improves cardiovascular and kidney health outcomes independent of diabetes in appropriate patient populations. SGLT inhibition decreases cardiovascular mortality and heart failure hospitalization independent of left ventricular ejection fraction. SGLT inhibitors reduce clinically relevant events such as dialysis and transplantation in CKD patients irrespective of etiology and are now a cornerstone for the prevention of CKD progression. The introduction of polypills in heart failure can simplify GDMT implementation. Show notes - The Data Supporting SGLT Inhibition with Dr. Muthiah Vaduganathan How did SGLT inhibitors transition from “diabetes medication” to guideline-directed cardiovascular medicine? Most therapies in cardiology were developed for a particular purpose and ended up being indicated for a vastly different reason. The SGLT-2 inhibitors are no different. Cardiovascular safety concerns about diabetes medications led to a mandate to conduct cardiovascular outcomes trials for all novel diabetes medications. This federal requirement shed light on the cardiovascular benefits of SGLT inhibitors in patients with diabetes. These initial trials showed that not only are these medications safe but also, surprisingly, proved their role in preventing heart failure and delaying progression of chronic kidney disease. What are the mechanisms of action of SGLT-2 and SGLT-1/2 inhibitors? The central mechanism(s) of how these medications confer health outcomes benefits patients is/are not well understood. The main organ involved in the action of SGLT-2 inhibitors is the kidney at the level of the proximal tubule, impacting the cardiovascular system by handling salt and water and improving kidney efficiency. Conversely, SGLT-1/2 inhibitors also act at the level of the gut, the predominant location of the SGLT-1 cotransporter. Their effects on the cardiovascular system are secondary, given there is no SGLT-1 or -2 cotransporters in the myocardium. These secondary effects can be impacted through blood pressure reduction, volume regulation, improved glycemic control, etc. to overall improve cardiovascular status. Whatever the underlying mechanisms, the empirical data for their use is strong and growing. What is the role of SGLT inhibitors in preventing CKD progression? RAAS inhibitors (ACE inhibitors and ARBs) have been the cornerstone of CKD management for the past two to three decades. SGLT inhibitors have been the first add-on to this background therapy. Four trials, DAPA-CKD, EMPA-CKD, CREDENCE, and the SCORED, investigated the effects of SGLT-2 and SGLT-1/2 inhibitors in patients with CKD with or without diabetes. The outcomes of these trials include modifying the course of CKD and reducing events such as dialysis initiation and transplantation. These effects were regardless of participants' diabetic status, CKD etiology, or individual patient profile.

CardioNerds (Drs. Gurleen Kaur and Richard Ferraro) and episode FIT Lead Dr. Saahil Jumkhawala (Cardiology Fellow at the University of Miami) discuss SGLT inhibitors, focusing on the biology of SGLT and its inhibition, with Dr. Katherine Tuttle (Executive Director for Research at Providence Healthcare, Co-Principal Investigator of the Institute of Translational Health Sciences, and Professor of Medicine at the University of Washington).  Show notes were drafted by Dr. Saahil Jumkhawala. The episode audio was engineered by CardioNerds intern Christiana Dangas. This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Lexicon Pharmaceuticals. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls - The Biology of SGLT Inhibition with Dr. Katherine Tuttle SGLT inhibitors, while initially developed as antidiabetic medications, have been shown to be beneficial for cardiovascular and renal outcomes. These benefits result from their on-target glucosuric effects and additional off-target effects. The side effect profiles of SGLTis are primarily mediated by glucose reabsorption in their target tissues. The side effect profile of SGLTis must be considered when prescribing these medications and is generally favorable for SGLT2is versus SGLT1is. Once SGLTis are prescribed, patients should be given specific attention to their eGFR, serum potassium, and clinical evaluations of volume status and blood pressure. Strategies to increase implementation of and reduce clinical inertia for these important class of medication remain an area of active investigation Show notes - The Biology of SGLT Inhibition with Dr. Katherine Tuttle What should prompt consideration of starting an SGLT inhibitor? Considerations for SGLT inhibitor initiation are based on a history of heart failure, kidney disease, and diabetes status. In the EMPA-KIDNEY trial, empagliflozin improved cardiovascular and kidney outcomes in those with low GFR (regardless of level of albuminuria). What is the mechanism of action of SGLT2 inhibitors? SGLT2 inhibitors improve glycemic control by blocking SGLT2 receptor-mediated reabsorption of glucose in the proximal convoluted tubule, where 80-90% of this reuptake occurs, and increased downstream excretion of glucose and sodium chloride. SGLT2 inhibitors provide only a modest glucose-lowering effect, particularly for patients with GFR

The Filtrate:Joel TopfSwapnil HiremathJosh WaitzmanNayan AroraSophia AmbrusoWith Special Guest:Brendon Neuen Super smart guy and clinical trialistVlado Perkovic Lead author of FLOW and friend of NephJCEditor Joel TopfShow NotesThe manuscript (NEJM): Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 DiabetesThe acronym FLOW from the title: evaluate renal Function with semagLutide Once Weekly (Twitter)Joel wrote a blog post prior to the FLOW publication to try to set the table: Peeking Inside Schrödinger's BoxBrendon's Neuen's tweet about total versus chronic slope (X | Twitter)Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity (Science Direct)Semaglutide and Diabetic Retinopathy Risk in Patients with Type 2 Diabetes Mellitus: A Meta-Analysis of Randomized Controlled Trials (PubMed)The Efficacy and Safety of the Combination Therapy With GLP-1 Receptor Agonists and SGLT-2 Inhibitors in Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis (Frontiers in Pharmacology)Statistical considerations for testing multiple endpoints in group sequential or adaptive clinical trials (PubMed)Proteinuria Thresholds Are Irrational: A Call for Proteinuria Indexing (Nephron Clinical Practice)Frank Harrel on why the NNT sucks (data methods)Regulation of Na+/H+ exchanger NHE3 by glucagon-like peptide 1 receptor agonist exendin-4 in renal proximal tubule cells (PubMed)Switching Between Glucagon-Like Peptide-1 Receptor Agonists: Rationale and Practical Guidance (PubMed)Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial (PubMed)Doctors are like the pyromaniac fireman (PBFluids)Suggest topics for NephMadness (Twitter)Design of the COmbinatioN effect of FInerenone anD EmpaglifloziN in participants with chronic kidney disease and type 2 diabetes using a UACR Endpoint study (CONFIDENCE) (PubMed)Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial (PubMed)Spitzer's involvement in revolutionizing nephrology is part of this lecture I did at the University of Nebraska Diabetes Symposium. (Dropbox: Start on slide 29)Spitzer Resigns, Citing Personal Failings (New York Times)Tubular Secretions Swap: Dumb Money on NetFlix (Wikipedia)Josh: Hiking Zion National Park (National Park Service)Sophia: Lost in Space 2018 TV series on NetFlix (Wikipedia)Nayan: Pelican Hill resort (Website)Joel: BodkinNephJC Summer Book Club: Covenant of Water by Abraham Verghese (Amazon)

Episode: May 2024 Host: Karl Steinberg, MD, HMDC, CMD Guest(s): Elizabeth Galik, PhD, CRNP (editor-in-chief); Nicole Orr, MD In This Episode: In this episode, host Dr. Karl Steinberg, MD, CMD, and editor-in-chief Dr. Elizabeth Galik, PhD, CRNP, discuss our May issue of Caring for the Ages with guest Nicole Orr, MD. This issue contains and special section on Heart Disease and Matters of the Heart. Dr. Orr, president of Post-Acute Cardiology Care, LLC, in Darien, CT, discusses the field of geriatric cardiology, including recent advancements and the need for collaboration with geriatricians and other post-acute and long-term care professionals. Dr. Galik also discusses three other articles in the special section: loneliness and heart disease, the importance of friendships amongst residents and how we can support residents to make friends, and a pragmatic research column on whether or not switching from warfarin to a novel oral anticoagulant is safer than remaining on warfarin in older, frail patients with atrial fibrillation. The findings are surprising! Be sure to check out the rest of this important special issue, including articles on women and heart disease, SGLT-2 Inhibitors, legal issues associated with cardiopulmonary resuscitation (CPR), and more! Featured Articles: Geriatric Cardiology: At the Forefront of Cardiovascular Care for Older Adults  SGLT-2 Inhibitors for the Management of Heart Failure  Loneliness and Heart Disease: What the Literature Tells Us and What We Can Do to Help Thank You for Being a Friend in Post-Acute and Long-Term Care To Switch or Not to Switch Anticoagulation? Date Recorded: May 2, 2024 Available Credit: The American Board of Post-Acute and Long-Term Care Medicine (ABPLM) issues CMD credits for AMDA On-The-Go and affiliate podcast episodes as follows: Claim CMD Credit

Diabetes medicine known as GLP-1 agonists and SGLT-2 inhibitors are recommended for people with type 2 diabetes in a recent large study that aggregated data from other studies. Rita Kalyani, a diabetes expert at Johns Hopkins, says while there's no … Are certain diabetes medicines best for specific people? Elizabeth Tracey reports Read More »

Conversation around patient selection and GLP-1 RAs. The speakers will explore the effects of GLP-1 RAs and SGLT-2 inhibitors on clinical outcomes and CVD risk factors.  Claim CE Credit at https://bit.ly/4aSgdzz  

It's In the News! A look at the top diabetes stories and headlines happening now. Top stories this week: A new study links emulsifiers, a common ingrediant, to type 2 diabetes, reserachers map out the pancreas in a new way that's already yielding new information, new guidliens about using GLP-1s and SGLT-2 medications with exisiting oral meds, genetic T1D studies and more!  Find out more about Moms' Night Out  Please visit our Sponsors & Partners - they help make the show possible! Learn more about Gvoke Glucagon Gvoke HypoPen® (glucagon injection): Glucagon Injection For Very Low Blood Sugar (gvokeglucagon.com) Omnipod - Simplify Life Learn about Dexcom  Edgepark Medical Supplies Check out VIVI Cap to protect your insulin from extreme temperatures Learn more about AG1 from Athletic Greens  Drive research that matters through the T1D Exchange The best way to keep up with Stacey and the show is by signing up for our weekly newsletter: Sign up for our newsletter here Here's where to find us: Facebook (Group) Facebook (Page) Instagram Twitter Check out Stacey's books! Learn more about everything at our home page www.diabetes-connections.com  Reach out with questions or comments: info@diabetes-connections.com

Let's Talk Diabetes and Prevention38 million Americans have diabetes (about 1 in 10).Approximately 98 million American adults -- that's 1 in 3, have prediabetes.More than 80% don't know they have it. The CDC reports that 18% of adolescents have prediabetes, and it's on the rise.Episode Notes00:15 - Who is Lara Al Dandachi?01:12 - Increase in Obesity and Diabetes03:40 - Type 1 vs Type 205:30 - Body Mass Index (BMI)07:10 - GLP-1 Antagonists - Ozempic, Wegovy11:38 - Ozempic and Pregnancy14:35 - IMPORTANT - Diabetes and Prediabetes16:45 - What are Beta Cells?22:35 - Food and Drink to Eliminate From Your Diet24:15 - Ultra-Processed Foods26:45 - Mediterranean Diet28:05 - Putting Diabetes into RemissionWhat Is Prediabetes?Prediabetes is a serious health condition. Blood sugar levels are higher than normal, but not yet high enough to be diagnosed as type 2 diabetes. With prediabetes, action is the best medicine.American Diabetes AssociationWhat is Diabetes?About 38 million Americans have diabetes (about 1 in 10), and approximately 90-95% have type 2 diabetes. Type 2 diabetes most often develops in people over age 45, but more and more children, teens, and young adults are also developing it.Preventing Type 2 DiabetesIf you have prediabetes, losing a small amount of weight if you're overweight and getting regular physical activity can lower your risk for developing type 2 diabetes.A small amount of weight loss means around 5% to 7% of your body weight, just 10 to 14 pounds for a 200-pound person.Regular physical activity means getting at least 150 minutes a week of brisk walking or a similar activity. That's just 30 minutes a day, five days a week.Tests for Diabetes and PrediabetesYour doctor will have you take one or more of the following blood tests to confirm the diagnosis:A1C TestThe A1C test measures your average blood sugar level over the past 3 months. An A1C below 5.7% is normal, between 5.7 and 6.4% indicates you have prediabetes, and greater than 6.5% indicates you have diabetes.Fasting Blood Sugar TestThis measures your blood sugar after an overnight fast (not eating). A fasting blood sugar level of 99 mg/dL or lower is normal, 100 to 125 mg/dL indicates you have prediabetes, and greater than 126 mg/dL indicates you have diabetes.GLP-1 Antagonists - Ozempic, Wegovy, Byetta, RybelsusThis class of drugs is commonly called glucagon-like peptide 1 (GLP-1) agonists.These drugs mimic the action of a hormone called glucagon-like peptide 1. When blood sugar levels start to rise after someone eats, these drugs stimulate the body to produce more insulin. The extra insulin helps lower blood sugar levels.Lower blood sugar levels are helpful for controlling type 2 diabetes. But it's not clear how the GLP-1 drugs lead to weight loss. Doctors do know that GLP-1s appear to help curb hunger. These drugs also slow the movement of food from the stomach into the small intestine.As a result, you may feel full faster and longer, so you eat less.Along with helping to control blood sugar and boost weight loss, GLP-1s and SGLT-2 inhibitors seem to have other major benefits. Research has found that some drugs in these groups may lower the risk of heart disease, such as heart failure, stroke and kidney disease. Source: The Mayo ClinicGuest Biography - Lara Al-DandachiLara Al-Dandachi is the Nutrition Director of the PRO (Program to Reduce Obesity) within the Division of Endocrinology at David Geffen School of Medicine and UCLA Health. Lara is a Registered Dietitian Nutritionist (RDN), Certified Diabetes Educator, and Obesity specialist who cares for patients in UCLA Health's Gonda Diabetes Center.She is one of very few Registered Dietitians in the nation who are triple board certified in diabetes care specialty CDCES, advanced diabetes management BC-ADM, and obesity and weight management subspecialty (CSOWM).Medical Board CertificationsAmerican Association of Diabetes Educators, 2016National Certification Board for Diabetes Educators, 2015Blackburn, Obesity Medicine, Harvard Medical School DegreesMPH, Loma Linda School of Allied Health, 2003BS in Nutrition & Dietetic, American University of Beirut About The Podcast HostTom Levine, leveraging a 25-year tenure in capital markets, leads Zero Hour Group and Native Angelino Real Estate, offering a suite of consulting, strategic analysis, and real estate services.An alumnus of USC Marshall School of Business and the Claremont Colleges - Pitzer College campus with a term at the London School of Economics. Additionally, he holds a CADRE broker's license (#02052698) and the designation certified Short Sale Specialist under the National Association of Realtors.Have a challenging transaction? Let's discuss. I consult on a range of transaction types and deal structures. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit www.1929.live

In his weekly clinical update, Dr. Griffin reviews recent statistics on the circulation of measles and influenza before addressing Vincent's comment on measles inclusion in the clinical respiratory PCR panel, the latest statistics on influenza and COVID-19 circulation, if inflammatory cytokines and anti-viral antibody function synergistically, if administration of peptide agonists of the glucagon-like or sodium-glucose pump can reduce disease severity, restates the guidelines for spring administration of COVID vaccines boosters, discusses the emergency use application of a pre-exposure prophylactic. revised guidelines for how to treat respiratory viral infection guidelines by the CDC, continues to dispel the myth of viral rebound, revised guidelines for SARS-CoV-2 treatment and how to treat respiratory viral infections, when to use steroids and the benefits of convalescent plasma, what do when healthcare workers succumb to SARS-CoV-2 infection, if remdesivir or paxlovid can reduce cardiovascular adverse events and the first finding of the two-year longitudinal study on long COVID. For more information about this body of work, listen to TWiV 1088. Subscribe (free): Apple Podcasts, Google Podcasts, RSS, email Become a patron of TWiV! Links for this episode Measles tracking (CDC) What happens when measles is included in commercial syndromic PCR panels (MMWR) Influenza/flu surveillance (CDC) Influenza on the Texas ranch (Statnews) Sequence analysis of highly pathogenic avian influenza from Texas (CDC) Influenza/flu map (CDC) COVID-19  hospital admissions (CDC) COVID-19 national trend (CDC) COVID-19 wastewater testing (biobot) Variant tracker (CDC) Variant hospital admissions (CDC) Can inflammatory cytokines and antibodies play nicely to prevent COVID-19 mortality (IJID) Association of GLP-1RA and SGLT-2i to modulate COVID-19 severity (Diabetes Therapy) Spring COVID-19 booster recommendations (CIDRAP) Older adult spring booster available (CDC) Advisory committee for immunization practices spring 2024 COVID-19 boosters (CDC) EUA for pemgarda (FDA) CDC Quarantine guidelines (CDC) NIH COVID-19 treatment guidelines (NIH) Molnupiravir safety and efficacy (JMV) Convalescent plasma recommendation for immunocompromised (IDSociety) CDC Quarantine guidelines (CDC) NIH COVID-19 treatment guidelines (NIH) What do when your heathcare provider is infected with SARS-CoV-2 (CDC) Managing healthcare staffing shortages (CDC) Steroids,dexamethasone at the right time (OFID) Anticoagulation guidelines (hematology.org) Remdesivir and cardiac adverse events in hospitalized patients (CID) Long COVID evidence based review TWiV shout out (TWiV 1088) Longitudinal study reveals long COVID symptom peaks and nadirs (OFID) Paxlovid lowers risk of cardiovascular disease in COVID-19 patients with autoimmune disease (BMC Medicine) Contribute to our ASTMH fundraiser at PWB Letters read on TWiV 1102 Dr. Griffin's COVID treatment summary (pdf) Timestamps by Jolene. Thanks! Intro music is by Ronald Jenkees Send your questions for Dr. Griffin to daniel@microbe.tv

Step up your diabetes game! Learn the ins and outs of continuous glucose monitors (CGM) including key features, what and how to order, interpreting CGM data (time in range, time above range, etc.), and how to make adjustments to a patient's insulin regimen, aka “insulin pattern matching”. We discuss common scenarios including overnight hypoglycemia, exercise-induced hypoglycemia, post-prandial hyperglycemia, what to do when the patient runs high all the time, and how to incorporate GLP1 agonists and SGLT2 inhibitors into a patient's regimen. Returning guest and Paul's favorite frenemy, Dr. Jeff Colburn (VCU Health) returns! Claim CME for this episode at curbsiders.vcuhealth.org! Patreon | Episodes | Subscribe | Spotify | YouTube | Newsletter | Contact | Swag! | CME Show Segments 00:00 Introduction and Diabetes Puns 01:00 Introduction of Guest and Topic 09:12 Qualifications and Eligibility for CGMs 11:32 Types of CGMs and Sensor Placement 24:47 Interpreting CGM Data and Alarms 34:30 Troubleshooting Patterns and Adjustments 35:23 Understanding Hypoglycemia and Counter Regulatory Hormone Responses 36:15 The Rule of 15 and Addressing Hypoglycemia 37:10 Reducing Basal Insulin to Address Nocturnal Hypoglycemia 38:29 Addressing Postprandial Highs with GLP-1, SGLT-2 Inhibitors, or Prandial Insulin 39:51 Managing Exercise-Induced Hypoglycemia 41:43 Preventing Exercise-Induced Hypoglycemia with Snacks 43:42 Managing Nocturnal Hypoglycemia with Sulfonylureas 45:31 Addressing Postprandial Hyperglycemia with GLP-1, SGLT-2 Inhibitors, or Prandial Insulin 46:54 Adjusting Basal Insulin to Address Morning Hyperglycemia 51:18 Troubleshooting High Blood Sugars with Basal Insulin and Mealtime Insulin 56:49 Managing High Blood Sugars with Basal Insulin and Mealtime Insulin 57:44 Addressing Adherence and Medication Barriers 59:39 Using Continuous Glucose Monitors (CGMs) for Diabetes Management 01:02:30 Using Sulfonylureas and Basal Insulin Combination as a Stopgap 01:05:49 Considering Patient Adherence and Barriers to Treatment Credits Writer and Producer: Matthew Watto MD, FACP Show Notes: Matthew Watto MD, FACP Cover Art and Infographic: Matthew Watto MD, FACP Hosts: Matthew Watto MD, FACP; Paul Williams MD, FACP    Reviewer: Emi Okamoto MD Showrunners: Matthew Watto MD, FACP; Paul Williams MD, FACP Technical Production: PodPaste Guest: Jeff Colburn MD Sponsor: Freed You can try Freed for free right now by going to freed.ai. And listeners of Curbsiders can use code CURB50 for $50 off their first month. Sponsor: Panacea Financial Download the 2024 Residents & Fellows Survey Report for free at panaceafinancial.com/report.

In this episode of Diabetics Doing Things, Rob interviews Brian Connelly from TheracosBio. Brian shares insights into his background, the mission of Theracos, and their breakthrough SGLT 2 inhibitor, Brenzavvy. The discussion delves into Brian's journey to Theracos, his work in the biotech industry, and the mission of Theracos to provide affordable medications for patients with common diseases, like type 2 diabetes. Topics discussed: 1. Brian Connelly's background and journey to TheracosBio. 2. The mission of TheracosBio to develop affordable medications for patients with chronic diseases. 3. Introduction to Theracos' breakthrough SGLT 2 inhibitor, Brenzavvy. 4. Challenges in the pharmaceutical industry regarding drug pricing and accessibility. 5. Impact of Brenzavvy on patients with type 2 diabetes, focusing on cost, efficacy, and improved health outcomes. 6. Distribution and accessibility of Brenzavvy through Cost Plus Drugs and traditional pharmacies. 7. The importance of alignment within the organization and the societal impact of providing affordable medications. 8. Addressing public health concerns, adherence rates, and long-term cost savings for patients with chronic conditions. Here are key takeaways and lessons: - TheracosBio is dedicated to providing affordable medications, like Brenzavvy, to patients with chronic diseases, such as type 2 diabetes. - Brenzavvy offers cost-effective treatment options with improved health outcomes for patients.- Share struggles to create awareness and support within the community. - The company's mission prioritizes patient access and affordability over maximizing profits, emphasizing societal impact and improved public health. - Collaboration with organizations like Cost Plus Drugs enhances distribution and accessibility of Brenzavvy to a wider patient population. - The importance of transparency, patient feedback, and physician awareness in promoting the use of affordable medications for chronic conditions. References: https://www.theracosbio.com/ https://www.brenzavvy.com 00:00: Unveiling the Noble Mission of TheracosBio: A Journey from Feline Diabetes to Human Therapeutics 05:59: Finding Purpose Through Chronic Illness and Work: A Journey of Passion and Perseverance 13:02: Revolutionizing Drug Pricing: The Mission of Theracos in Making Medication Accessible 19:37: Exploring the High Cost of Diabetes Medication and Solutions 24:28: Addressing Societal Impact and Accessibility in Diabetes Treatment 29:16: Challenges and Misconceptions in the Pharmaceutical Industry 33:45: Building a Mission-Driven Company: The Journey of Theracos CEO 37:57: Revolutionizing Access to Medication: The Success Story of Brenzavvy 40:58: Unveiling Brenzavvy: The Affordable and Effective SGLT 2 Inhibitor for Type 2 Diabetes 45:06: Revolutionizing Healthcare with Low Cost Drugs: A Story of Passion and Purpose

Diabetes Core Update is a monthly podcast that presents and discusses the latest clinically relevant articles from the American Diabetes Association's four science and medical journals – Diabetes, Diabetes Care, Clinical Diabetes, and Diabetes Spectrum. Each episode is approximately 25 minutes long and presents 5-6 recently published articles from ADA journals. Intended for practicing physicians and health care professionals, Diabetes Core Update   discusses how the latest research and information published in journals of the American Diabetes Association are relevant to clinical practice and can be applied in a treatment setting. Welcome to diabetes core update where every month we go over the most important articles to come out in the field of diabetes. Articles that are important for practicing clinicians to understand to stay up with the rapid changes in the field.  This issue will review: 1.     Leisure-time physical activity may attenuate the impact of diabetes on cognitive decline in middle-aged and older adults 2.     Outcomes of SGLT-2i and GLP-1RA Therapy Among Patients With Type 2 Diabetes and Varying NAFLD Status 3.     Sodium-Glucose Cotransporter 2 Inhibitors and Nephrolithiasis Risk in Patients With Type 2 Diabetes 4.     Association of body weight time in target range with the risk of kidney outcomes in patients with overweight/obesity and type 2 diabetes mellitus 1 Diabetes 5.     Modifiable Lifestyle Factors, Genetic Risk, and Incident Peripheral Artery Disease among Individuals with Type 2 Diabetes   For more information about each of ADA's science and medical journals, please visit www.diabetesjournals.org. Hosts: Neil Skolnik, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Associate Director, Family Medicine Residency Program, Abington Jefferson Health John J. Russell, M.D., Professor of Family and Community Medicine, Sidney Kimmel Medical College, Thomas Jefferson University; Director, Family Medicine Residency Program, Chair-Department of Family Medicine, Abington Jefferson Health

CardioNerds Dr. Rick Ferraro (CardioNerds Academy House Faculty and Cardiology Fellow at JHH), Dr. Gurleen Kaur (Director of the CardioNerds Internship and Internal Medicine resident at BWH), and Dr. Alli Bigeh (Cardiology Fellow at the Ohio State) as they discuss the growing obesity epidemic and how it relates to cardiovascular disease with Dr. Ambarish Pandey (Cardiologist at UT Southwestern Medical Center). Show notes were drafted by Dr. Alli Bigeh. CardioNerds Academy Intern and student Dr. Shivani Reddy performed audio editing. Obesity is an important modifiable risk factor for cardiovascular disease, and it is on the rise! Here, we discuss how to identify patients with obesity and develop an approach to address current lifestyle recommendations. We also discuss the spectrum of pharmacologic treatment options available, management strategies, and some therapy options that are on the horizon. This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Novo Nordisk. See below for continuing medical education credit. Claim CME for this episode HERE. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - Lifestyle & Pharmacologic Management of Obesity Identify obese patients not just using BMI, but also using anthropometric measurements such as waist circumference (central adiposity). Lifestyle modifications are our first line of defense against obesity! Current recommendations emphasize caloric restriction of at least 500kcal/day, plant-based and Mediterranean diets, and getting at least 150 minutes of moderate-intensity weekly exercise. Dive into the root cause of eating and lifestyle behaviors. It is crucial to address adverse social determinants of health with patients to identify the driving behaviors, particularly among those individuals of low socioeconomic status. Newer weight loss agents are most effective at achieving and maintaining substantial weight loss, in particular Semaglutide (GLP-1) and Tirzepatide (GLP-1/GIP). Initiate at a low dose and titrate up slowly. Obesity is a risk factor and potential driver for HFpEF. Targeted treatment options for obese patients with HFpEF include SGLT-2 inhibitors and semaglutide, which recently showed improvement in quality of life and exercise capacity in the STEP-HFpEF trial. Show notes - Lifestyle & Pharmacologic Management of Obesity How do we identify and define obesity? The traditional definition of obesity is based on body mass index (BMI), defined as BMI greater than or equal to 30.0 kg/m2 (weight in kg/height in meters).Recognize that BMI may not tell the whole story. A limitation of BMI is it does not reflect differences in body composition and distribution of fat.Certain patients may not meet the BMI cutoff for obesity but have elevated cardiovascular risk based on increased central adiposity, specifically those that are categorized as overweight.The devil lies in the details of anthropometric parameters. Include waist circumference measurements as part of an obesity assessment of visceral adiposity. A waist circumference greater than 40 inches for men and greater than 35 inches for women is considered elevated. What are some current lifestyle recommendations for obese patients? Lifestyle recommendations are the first line of defense against obesity.Current ACC/AHA guidelines suggest a target of reducing caloric intake by 500 kcal per day. For patients with severe obesity, this number may be higher.Emphasis on hypocaloric plant-based and Mediterranean dietsReduce total carbohydrate intake to 50-130 grams per day.Focus on a low-fat diet with less than 30% of total energy coming from fat with a high-protein diet to main...

Embark on a journey into the future of health and fitness as we unveil the groundbreaking trends anticipated to revolutionize well-being in 2024. In this episode, we explore predictions ranging from the rise of innovative weight loss drugs to the integration of artificial intelligence in personalized fitness plans. Join us for a compelling discussion with valuable insights, expert opinions, and a glimpse into what the future holds for your health. Key Topics: Cutting-Edge Weight Loss Drugs: Explore the evolving landscape of weight loss drugs, including DPP-4 Inhibitors, SGLT-2 Inhibitors, combination therapies, and more. Discuss the potential trends in muscle preservation and its impact on the health and fitness industry. Virtual and Augmented Reality Workouts: Dive into the world of virtual and augmented reality workouts, examining the pros and cons. Discover how technology may reshape the fitness experience, offering motivation and convenience while addressing potential challenges. Aging as a Preventable Disease: Shift your perspective on aging as we explore primary prevention methods, life span trends, and innovative approaches to address aging-related concerns. Delve into the latest advancements in preserving muscle mass, detecting cancer, dementia prevention, and more. AI in Personalized Fitness Plans: Uncover the integration of artificial intelligence in crafting personalized fitness plans. Explore the benefits and potential drawbacks of AI, from efficiency gains to data privacy concerns. Precision Healthcare and AI Predictions: Journey into the future of healthcare with CRISPR and gene editing, 3D printing of implants, and personalized pharmaceuticals. Discuss the accessibility and prediction models of AI in shaping personal health trends. Functional Health Practitioners' Downfall: Witness the transformation in trust dynamics within the fitness industry, questioning the validity of functional health methodologies. Anticipate the rise of evidence-based practices and the empowerment of individuals through informed decision-making. Don't miss this captivating episode as we navigate through the exciting landscape of health and fitness trends, providing you with insights that will empower your well-being in 2024 and beyond! Coach VinnyEmail: vinny@balancedbodies.ioInstagram: vinnyrusso_balancedbodiesFacebook: Vinny Russo Dr. ErynEmail: dr.eryn@balancedbodies.ioInstagram: dr.eryn_balancedbodiesFacebook: Eryn Stansfield LEGION 20% OFF CODEGo to https://legionathletics.com/ and use the code RUSSO for 20% off your order!

Eric and Jess are back with the first SGLT of 2024! They will be discussing the best April Fools joke of all time, The Murder of Sonic the Hedgehog! This is a free game that tasks you with discovering who killed the blue blur! Come with us as we discuss one of the best visual novels of 2023! Follow the Official Short Game Long Talk Threads and Instagram! https://www.threads.net/@shortlongpod https://www.instagram.com/shortlongpod/ https://twitter.com/ShortLongPod Join our Discord! https://discord.gg/JU2reNuzaU Also follow Eric and Jess on Threads! https://www.threads.net/@mr_the_human https://www.threads.net/@_.jess.ron https://twitter.com/MrTheHuman Theme Music Credit Dark Flashes by Shane Ivers - https://www.silvermansound.com

Neste sétimo episódio em podcast da Série Diabetes – Baseado em evidências, Luiz Fernando Vieira, médico endocrinologista e conteudista do Portal, fala sobre as evidências mais atuais a respeito dos benefícios renais do uso de inibidores de SGLT-2, tanto em pessoas com diabetes como em indivíduos com doença renal crônica não diabética. Ouça agora! A nova série Diabetes – Baseado em evidências tem por objetivo realizar uma ampla revisão baseada nas mais recentes evidências para atualizar os médicos sobre diferentes aspectos da diabetes. Essa doença, que é um dos maiores problemas de saúde mundial, apresenta impactos em todos os sistemas do organismo, por isso conhecê-la a fundo permitirá que o médico aperfeiçoe seu atendimento e tenha um melhor resultado terapêutico. Não deixe de conferir os próximos episódios! Confira esse e outros posts no Portal PEBMED e siga nossas redes sociais! Facebook Instagram Linkedin Twitter

Calling all those with a passion for cardiovascular prevention! In this episode of the CardioNerds Cardiovascular Prevention Series, we take a deep dive into the world of glucagon-like peptide-1 (GLP-1) receptor agonists. Along the way, you'll hear about the biology of the GLP-1 molecule and its related peptides, learn more about how GLP-1 agonists promote glycemic control, weight loss, and cardiometabolic health, and explore the current body of literature supporting the individualized application of these medications to patients with diabetes, obesity, and/or ASCVD. Join Dr. Christian Faaborg-Andersen (CardioNerds Academy Fellow and Internal Medicine Resident at MGH), Dr. Gurleen Kaur (Director of the CardioNerds Internship, Chief of House Einthoven, and Internal Medicine resident at BWH), and Dr. Rick Ferraro (CardioNerds Academy House Faculty and Cardiology Fellow at JHH) for a wide-ranging discussion on GLP-1 and GIP agonists with Dr. Dennis Bruemmer (Cardiologist and Director of the Center for Cardiometabolic Health in the section of Preventive Cardiology at the Cleveland Clinic). Show notes were drafted by Dr. Christian Faaborg-Andersen. Audio editing was performed by CardioNerds Academy Intern, student Dr. Tina Reddy. This episode was produced in collaboration with the American Society of Preventive Cardiology (ASPC) with independent medical education grant support from Novo Nordisk. See below for continuing medical education credit. CardioNerds Prevention PageCardioNerds Episode PageCardioNerds AcademyCardionerds Healy Honor Roll CardioNerds Journal ClubSubscribe to The Heartbeat Newsletter!Check out CardioNerds SWAG!Become a CardioNerds Patron! Pearls and Quotes - GLP-1 Agonists: Mechanisms to Applications The selection and dosing of GLP-1 and GIP agonists (GLP-1s and GIPs) depends on their intended use as an anti-glycemic or anti-obesity agent. The cardiovascular benefits of GLP-1s and GIPs may be independent of improvements in glycemic control, and in part be driven by reduction in inflammation, a key driver of arterial plaque formation. In patients with comorbid coronary artery disease, obesity, and diabetes, GLP-1 agonists and SGLT-2 inhibitors should be used as first-line agents, over metformin. Tirzepatide is a dual agonist that activates GIP and GLP-1 receptors. GIP is highly expressed in the brain, which may mediate satiety, promote energy expenditure, and enhance peripheral glucose metabolism. Caution should be used with GLP-1 agonists in patients with long-standing diabetes complicated by gastroparesis, as well as incompletely treated diabetic retinopathy. GI upset is not uncommon with GLP-1/GIP agonists, and switching to a different agonist is unlikely to help.  Show notes - GLP-1 Agonists: Mechanisms to Applications What are the mechanisms of action by which GLP-1 and GIP controls blood sugar and body weight? Glucagon-like peptide-1 (GLP-1) is an endogenous hormone that is secreted in response to an oral glucose load. It promotes insulin release, inhibits glucagon secretion, and slows gastric emptying via the brain-intestine axis, leading to satiety. GLP-1 agonists are medications that mimic the effect of this hormone and, on average, lower hemoglobin A1C by 0.8% to 1.5%. These medications include semaglutide, liraglutide, and dulaglutide. Glucose-dependent insulinotropic polypeptide (GIP) is also an endogenous hormone, similarly secreted by the body in response to an oral glucose load such as a meal. GIP is highly expressed in the arcuate nucleus and hypothalamus, which may mediate satiety, promote energy expenditure, and enhance peripheral glucose metabolism. Tirzepatide is a dual GLP-1/GIP agonist. What is the role of GLP-1/GIP agonists in patients with overweight/obesity and/or type 2 diabetes? How does the dosing of GLP-1/GIP medications change with their intended disease target?

Joining Brian and myself in our studio (again, that is two in a row) we delighted to speak to Chris Scudder, Senior Lecturer in Internal Medicine and Co-Head of the Internal Medicine Team here at the RVC. There has been a couple of new drugs on the market one in the USA (bexagliflozin) and one in the UK (velagliflozin) both SGLT-2 inhibitors, oral hypoglycaemic agents to be used in newly diagnosed diabetic cats. We thought we’d chat to Chris about the information that is out there about these agents, how they can be used and what questions we have about their use. He recently spoke to our ECC team about euglycaemic diabetic ketoacidosis (eDKA) and I was intrigued. We hope that you enjoy. Some references:  https://pubmed.ncbi.nlm.nih.gov/37148170/  https://pubmed.ncbi.nlm.nih.gov/34975223/  There is an abstract on page 2512 here https://onlinelibrary.wiley.com/doi/10.1111/jvim.16559 To Cite this podcast as: Dom Barfield. RVC Clinical Podcast 140 Oral hypoglycaemic drugs for diabetic cats with Chris Scudder. Published on Dec 15 2023  If you have any comments about this podcast, please get in touch: email podcast@rvc.ac.uk or follow us on instagram @rvcclinicalpodcast. We would greatly appreciate your time to rate us on Apple podcast, podbean or Acast and kindly write us a review.

View the Show Notes Page for This Episode Become a Member to Receive Exclusive Content Sign Up to Receive Peter's Weekly Newsletter In this “Ask Me Anything” (AMA) episode, Peter explores various pharmacologic tools commonly utilized to improve metabolic health and treat diabetes, including SGLT-2 inhibitors, metformin, and GLP-1 agonists. He examines the available data on these drugs, assessing their comparative effectiveness and their potential in the context of lifestyle interventions. Additionally, he offers insights into whether SGLT2 inhibitors hold promise as geroprotective agents beyond their effects on glycemic control. Next, Peter analyzes the relationship between statin usage and the risk of developing insulin resistance and type 2 diabetes, investigating possible causal pathways and providing insights into strategies for risk reduction. He offers insights on monitoring adverse statin effects and evaluating the need for adjustments, ultimately weighing the trade-off between the risk to overall metabolic health against the benefits of reducing apoB levels through statin use. If you're not a subscriber and are listening on a podcast player, you'll only be able to hear a preview of the AMA. If you're a subscriber, you can now listen to this full episode on your private RSS feed or our website at the AMA #53 show notes page. If you are not a subscriber, you can learn more about the subscriber benefits here. We discuss: Pharmacologic tools for improving metabolic health, and the relationship between statins and insulin resistance [2:00]; SGLT-2 inhibitors: how they work and help to manage type 2 diabetes [4:15]; The history of SGLT2 inhibitors – from discovery to the current state [10:15]; Comparing the various FDA-approved SGLT2 inhibitors [15:00]; Other beneficial effects of SGLT2 inhibitors outside of glycemic control [20:15]; Exploring SGLT2 inhibitors as potential geroprotective molecules [22:45]; The side effects and risks associated with SGLT2 inhibitors [31:45]; Medications, lifestyle interventions, and other considerations for treating diabetes and improving metabolic health [37:45]; Metformin as a tool for pre-diabetics, and how metformin compares to lifestyle interventions [44:00]; How GLP-1 agonists compare to metformin and SGLT2 inhibitors in terms of glycemic control and weight loss [49:15]; Exploring the relationship between statin use and the risk of developing insulin resistance and type 2 diabetes [52:30]; Possible mechanisms of statin-induced insulin resistance and diabetes, and potential mitigation strategies [1:04:30]; How to monitor for adverse effects of statin use and assess the need for adjustments [1:11:45]; Weighing the benefits and risks of statin use: does the diabetes risk outweigh the benefits of lowering apoB with a statin? [1:15:30]; Parting thoughts [1:20:45]; and More. Connect With Peter on Twitter, Instagram, Facebook and YouTube

Episode 154: Heart Failure and GDMTDr. Malave explains the four main medications that are part of the guideline-directed medical therapy of heart failure with reduced ejection fraction. Dr. Arreaza added comments and questions.  Written by Maria Fernanda Malave, MD. Edits by Hector Arreaza, MD.  You are listening to Rio Bravo qWeek Podcast, your weekly dose of knowledge brought to you by the Rio Bravo Family Medicine Residency Program from Bakersfield, California, a UCLA-affiliated program sponsored by Clinica Sierra Vista, Let Us Be Your Healthcare Home. This podcast was created for educational purposes only. Visit your primary care provider for additional medical advice.Brief introduction: Heart failure (HF) is a common condition that affects about 23 million people in the world, and it is estimated that 50% of cases are due to heart failure with reduced ejection fraction (HFrEF). It is a major public health concern because of the high morbidity and mortality with a 5-year survival rate of 25% after hospitalization due to HFrEF.In recent years, the management of HFrEF has evolved due to increased evidence in favor of certain medications. Guideline-directed medical therapy (GDMT) is the foundation of medical therapy for these patients, and it is the result of multiple randomized controlled trials and reviews favoring four main drug classes: 1. renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors -ACEi- and angiotensin receptor blockers -ARB), 2. evidence-based β-blockers, 3. mineralocorticoid inhibitors, and 4. sodium-glucose cotransporter 2 inhibitors -SGLT-2i-. The benefit of this therapy is mostly seen when these four groups of medications are used in conjunction. During this episode, we will provide some key elements about the prescription of these medications, but this is only an overview, and you are invited to continue learning from reputable sources.Definitions: HF is defined as the impairment of the heart to meet the metabolic demands of the body. It can be caused by multiple conditions that interfere with the filling up of the heart or conditions that prevent an effective ejection of blood out of the heart. Classification of HFrEF: Based on the EF by echocardiogram, heart failure can be classified as:Heart failure with preserved ejection fraction (HFpEF) when the EF is 50% or more.Heart failure with mildly reduced ejection fraction when EF ranges between 41-49%.Heart failure with reduced ejection fraction (HFrEF) when EF is 40% or less.GDMT: Once we make the diagnosis of HF, it is key to educate our patients and re-educate them every single visit about the importance of guideline-directed medical therapy (GDMT) and lifestyle modifications, because this can change the prognosis and exacerbation rates. Many patients think that since they are feeling well after starting GDMT they can stop it, but that's going to increase exacerbations, hospitalizations, and decrease quality of life. Key points to discuss with patients.First, discuss that GDMT are disease-modifying drugs that regulate the neurohormonal system to stop the progression of the disease. We should explain to our patients that medications should be taken despite feeling well. Also, patients should be educated about regular follow-ups and medication titration. We can even instruct our patients about increasing their furosemide dose if they observe signs of overload, such as a weight increase of 2-3 kgs in 3-4 days, tight rings, socks or bracelets, also Paroxysmal nocturnal dyspnea, dyspnea on exertion, and more.  Second, lifestyle modifications such as: quit smoking and alcohol. Additionally, in general, water restriction between 1.2-1.5L daily, salt restriction (there is no official recommendation about how many grams, but in general we recommend less than 2g daily). Third, it is highly recommended to do aerobic exercise that produces mild dyspnea since this improves cardiovascular capacity and decreases hospitalization risk. Patients should be encouraged to have their annual influenza vaccine and pneumococcal vaccine according to their own immunization schedule. According to the AFP journal, in September 2022, researchers found a clinically and statistically significant reduction in all-cause mortality for patients who received an influenza vaccine right after an MI, with a number needed to treat of 50, the effectivity of the vaccine may vary by season.GDMT, groups of medications:What are the basic medications any patient with HF should be on? At least, patients should be on angiotensin receptor blockers ARBs/ACEIs and Beta-blockers. Let's keep in mind that beta-blockers should be given cautiously in cases of exacerbation, but in general low doses are safe. We also have the angiotensin receptor/neprilysin inhibitors (ARNIs), a group of medications whose representative is the combination of sacubitril/valsartan, aka Entresto®. This medication should be the target once ARBs/ACEIs are tolerated. ARBs/ACEIs/ARNIs should be discontinued in the setting of advanced CKD, with a GFR of 30 or less. This applies to other medications used in HF such as SGLT-2 and mineralocorticoid receptor antagonist (MRA, such as spironolactone/eplerenone). Remember that SGLT-2 inhibitors should be started regardless diabetes status, and BB are safe in the setting of CKD. We also have other groups that are considered safe in patients with advanced CKD such as hydralazine/isosorbide dinitrate (combined or not), which are used in African Americans whose BP and HF symptoms do not improve with maximally tolerated dose of ARBs/ACEIs + BB.Ivabradine: Let's not forget about ivabradine, which is an SA node inhibitor like BB. Patients need to meet criteria such as a maximally tolerated dose of beta-blocker, heart rate of a least 70 or more and being on normal sinus rhythm to be started on this medication. Ivabradine does not improve survival as BB do, so even though they are not contraindicated in HF exacerbation, BB are still preferred since ivabradine does not decrease mortality.Titration and follow-ups in the HF management:-ARBs/ACEIs/ARNIs should be titrated approx. Q2 weeks until the maximally tolerated dose is achieved, ARNI should be titrated up Q2-4weeks. With these medications, we should monitor BP, potassium levels and Glomerular Filtration Rate (GFR). -BB can also be titrated up Q2weeks until the maximally tolerated dose is achieved. HR, BP and signs of congestion should be observed in patients on BB. Same for hydralazine/isosorbide, with BP follow-up. -MRA, such as spironolactone/eplerenone, these meds can be added in patients who remain symptomatic despite maximally tolerated doses of “ARBs or ACEIs or ARNIs” plus Beta-blockers. For MRA, potassium level, and GFR should be monitored every 2-3 days after initiation, 7 days after titration, monthly for 3 months, and then Q3 months. To start a patient on MRA, K+ must be lower than 5.Patients with HF should be followed up at least in a 2-week interval either via telephone, telemedicine, or clinic visit to assess symptoms, vital signs, bloodwork and to perform a physical exam. Monitoring EF: After 3-6 months of the patient´s stabilization, we should reorder an echo, EKG, BNP and Basic Metabolic Panel. The ejection fraction improves in all patients after GDMT initiation and compliance, and in some patients, this improvement is very significant, so we need to reassess EF after stabilization. Comorbidities: Also, let´s keep in mind that most of the patients have associated comorbidities such as Afib, diabetes, valve disease, or anemia. These comorbidities must be addressed either by starting anticoagulation, adjusting anti-diabetes medications, starting iron, or referring to cardiology if a valve replacement is needed.When to refer to Cardiology? Some patients will qualify for device therapy (ICD) as a primary prevention for ventricular arrhythmias that can degenerate either into torsades or ventricular fibrillation. These patients must be symptomatic, at least in 3 months of maximally tolerated GDMT, and EF between 30-35%. Symptomatic

Ozempic is the latest weight-loss craze sweeping the world, and with good reason: it really is providing results. But is this "miracle" drug as miraculous as it seems to be? In this episode, you'll learn: - what Ozempic and Wegovy actually do inside your body - the potential pros and cons of taking this peptide - why Ozempic isn't a magic weight-loss drug - alternative options to Ozempic to help you lose weight ... and more! Show Notes: Schedule a 1:1 Discovery Call with me! Coursework from Master's in Human Nutrition & Functional Medicine Program at the University of Western States Efficacy and safety of GLP-1 receptor agonists versus SGLT-2 inhibitors in overweight/obese patients with or without diabetes mellitus: a systematic review and network meta-analysis Link Between Ozempic and Gallbladder Disease? Ozempic Goes Way Off-Label Once-Weekly Semaglutide in Adults with Overweight or Obesity Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review What Is Ozempic and Why Is It Getting So Much Attention? Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension For Those With Eating Disorders, Ozempic Can Be A Triggering Nightmare Boosting GLP-1 by Natural Products GLP-1 Supplements Weight Loss Medications: GLP-1 Agonists and How They Work Get my Core-Gi Workout Program with the 15% off listener discount You can learn more about me by following on IG or Tiktok @imperfectlypaigewellness or by checking out my blog, freebies, and offers on my website: https://imperfectlypaigewellness.com Please share with #PaigeTalksWellness to help get the word out about the show - and join the Imperfect Health Fam over on Facebook.

Welcome to Protecting Your Nest with Dr. Tony Hampton. Dr. Mariela Glandt, a Harvard and Columbia-educated endocrinologist, has extensive experience in treating diabetes. She is the founder and director of Glandt Center for Diabetes Care, which uses the ketogenic diet as its main therapeutic tool. Dr. Glandt has worked in New York, both in a private clinic and at Mount Sinai Hospital. In Israel, she worked as the director of the Clinical Research Unit for Diabetes at Hadassah Ein Kerem University Medical Center.  Dr. Glandt publishes articles in international journals, is involved in clinical trials, and continues to mentor interns at Bronx Hospital in New York. She is a co-founder of Eatsane, which produces low-carb food with no artificial sweeteners. In addition, she is a co-founder of Metabolix, a non-profit organization that aims to educate people to help them achieve optimal metabolic health. In this discussion, Drs. Tony and Mariela talk about: (04:27) Israel—it's culture and food (12:20) Dr. Mariela's career path and the development of  her interest in the ketogenic/low-carb diet (17:05) Why insulin is not the answer for Type 2 diabetes (27:02) How to get a Type 2 patient off of insulin safely and productively (31:31) The SGLT category of medications (37:45) How to meet people where they are at in order to help them succeed on a low-carb diet (42:55) How to get specialists and doctors interested and educated about low-carb and metabolic health (47:41) Dietary guidelines in Israel (48:08) The incredible benefits of the carnivore diet Thank you for listening to Protecting Your Nest. For additional resources and information, please see the links below.   Links:   Dr. Mariela Glandt: The Glandt Center for Diabetes Care Twitter Instagram OWNA Health   Dr. Tony Hampton: Linktree Instagram Account LinkedIn Account Ritmos Negros Podcast Q Med Symposium for Metabolic Health Lectures How Waking Up Every Day at 4:30 Can Change Your Life

Welcome back Rounds Table Listeners! In this throwback episode, Mike and John explore two papers exploring the use of SGLT-2 Inhibitors in heart failure. Check it out below! Efficacy and Safety of Dapagliflozin According to Frailty in Heart Failure With Reduced Ejection Fraction (0:00 – 7:20). SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis ...The post TBT – SGLT-2 Inhibitors in Heart Failure appeared first on Healthy Debate.

Welcome back Rounds Table Listeners! In this throwback episode, Mike and John explore two papers exploring the use of SGLT-2 Inhibitors in heart failure. Check it out below! Efficacy and Safety of Dapagliflozin According to Frailty in Heart Failure With Reduced Ejection Fraction (0:00 – 7:20). SGLT-2 inhibitors in patients with heart failure: a comprehensive meta-analysis ... The post TBT – SGLT-2 Inhibitors in Heart Failure first appeared on Healthy Debate. The post TBT – SGLT-2 Inhibitors in Heart Failure appeared first on Healthy Debate.

Have you noticed that your patients are being prescribed SGLT-2 inhibitors, even if they don't have diabetes?  If your patient asked, would you be able to explain why they are taking an SGLT-2 inhibitor?Listen in to learn about how this new and fascinating class of medication that was designed for diabetes is now being prescribed for heart failure, too.Check out Nicole Kupchik's exam reviews and practice questions at nicolekupchikconsulting.com. Use the promo code UPMYGAME20 to get 20% off all products.See the show notes at upmynursinggame.com.

What about oral?? Lewis GD et al. Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: The IRONOUT HF randomized clinical trial. JAMA 2017 May 16; 317:1958. (http://dx.doi.org/10.1001/jama.2017.5427. opens in new tab) randomized, 225 patients with symptomatic systolic HF for 16-weeks to either  oral iron polysaccharide 150 mg twice daily and placebo in 225 patients with symptomatic systolic HF (median left ventricular ejection fraction, 25%) At 16 weeks, the groups did not differ on the primary endpoint of peak oxygen consumption (VO2) or on secondary endpoints, including 6-minute walk distance and quality of life as measured with the Kansas City Cardiomyopathy Questionnaire. Thus as you mentioned not only is it not well tolerated it also doesn't appear to work which might be a better reason to not give it.https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0279166Vitamin D2 supplementation was associated with a 48.8% reduction in suicide/self-harm risks, and vitamin D3 with a 44.8% reduction, both highly significant (P < .001).   this sounds great but it is purely relative reduction not absolute because the absolute numbers wereUnadjusted suicide attempt/intentional self-harm rates in the D2 sample were 0.27% for those treated versus 0.52% for those untreated. The corresponding percentages for D3 were 0.20% versus 0.36%, respectively.Which equals a NNT of roughly 400 and 625 over 8 yrs, respectfully.IF this was true then that actually isn't too bad (not good or great but not terrible) but this was a retrospective observational trial so they just looked at a lot of people and said what can we find and publish.So what are other reasons that someone would not commit suicide??My first thought is ‘you only get put on vit d if you go to the doctor” (which is true)And typically the people that go to the doctor for their health care a little more about their health than someone who commits suicideClearly this isn't a universal answer but possibleAnother thought isthe vet that goes to the doctor and gets prescribed vit d feels like someone “cares for him/her” so maybe it has nothing to do with the vit d but just the sense of reassurance that someone cares about them?? Based on this I still wouldn't/wont write for vitamin d unless you need cheap placebo since we cant actually write for placeboD'Andrea E et al. Comparing effectiveness and safety of SGLT2 inhibitors vs DPP-4 inhibitors in patients with type 2 diabetes and varying baseline HbA1c levels. JAMA Intern Med 2023 Feb 6; [e-pub]. Sodium–glucose cotransporter-2 (SGLT-2) inhibitors are used to manage type 2 diabetes but also have protective cardiovascular and renal effects.  Do these benefits and adverse effects vary according to baseline level of hyperglycemia SGLT-2 inhibitors were compared with propensity-score–matched patients who initiated dipeptidyl peptidase-4 (DPP-4) inhibitors, within three categories of HbA1c: 9%. After mean follow-up of 8 months, initiation of SGLT-2 inhibitors was associated with significantly lower risks for major adverse cardiovascular events and hospitalization for heart failure, DUH we know this works in people that don't have diabetes why is it a surprise that it works in those with uncontrolled or controlled diabetes. To me this points to the problem that A1C is a number, it is not the problem, a bad A1C says there could be a problem in the future but in itself the A1C is a number!Buelt, Andrew | Apr 19, 2023, 3:25 PM | | to meTreat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial | Cardiology | JAMA | JAMA Network JAMA. 2023;329(13):1078-1087. doi:10.1001/jama.2023.2487  randomized noninferiority trial 4400 patients Question  Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease? To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.  Which isn't HIGH in my book that that is fine.  Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. The primary end point occurred in (8.1%) in the treat-to-target group and (8.7%) in the high-intensity statin group  Worst conclusion ever“Conclusions and Relevance  Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.” Let's see if something that's much more difficult and costly and more blood draws and more work and more office appointments is non inferior to something that's easier such as take this medication and that it………………………………... Then why it is, we recommend the much more difficult thing.     Treat-to-Target or High-Intensity Statin in Patients With Coronary Artery Disease: A Randomized Clinical Trial | Cardiology | JAMA | JAMA Network JAMA. 2023;329(13):1078-1087. doi:10.1001/jama.2023.2487  randomized noninferiority trial 4400 patients Question  Is treatment to a goal low-density lipoprotein cholesterol (LDL-C) level between 50 and 70 mg/dL noninferior to a strategy using high-intensity statin therapy among patients with coronary artery disease? To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease.Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg.  Which isn't HIGH in my book that that is fine.  Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points. The primary end point occurred in (8.1%) in the treat-to-target group and (8.7%) in the high-intensity statin group  Worst conclusion ever“Conclusions and Relevance  Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy.” Let's see if something that's much more difficult and costly and more blood draws and more work and more office appointments is non inferior to something that's easier such as take this medication and that it………………………………... Then why it is, we recommend the much more difficult thing.        Hydrochlorothiazide and Prevention of Kidney-Stone Recurrence | NEJMN Engl J Med 2023; 388:781-791  Thiazide diuretic agents are widely used for prevention of the recurrence of kidney stones, but data regarding the efficacy of such agents as compared with placebo are limited.  double-blind RCT  patients with recurrent calcium-containing kidney stones were randomized to hctz 12.5 mg, 25 mg, or 50 mg once daily or placebo once daily.  primary end point, a composite of symptomatic or radiologic recurrence of kidney stones. Symptomatic= The visible passage of a stone and radiologic =Appearance of new stones on CT 416 patients were randomized and followed for almost 3yrs primary end-point event occurred in (59%) in the placebo group (59%) in the 12.5-mg hydrochlorothiazide group (56%) in the 25-mg group(49%) in the 50-mg group  (rate ratio, 0.92; 95% CI, 0.63 to 1.36) No difference in any of the subgroups that was looked at there was no difference in the stone composition if it was calcium oxalate or calcium phosphate there was no difference Some women and people of race were underrepresented in this study but when you have a well done study that is the best we have the burden of proof now falls on you to prove there is benefit… for me this goes against board questions and what I thought was true and will lead me to stopping HCTZ if I am using it for prevention of kidney stones.