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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. 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 - 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?

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Your gut bacteria are your secret weight loss tool!! There has been a lot of hype surrounding the new GLP-1 agonist medications ,(Semaglutide, Wegovy, Ozempic, etc) due to their profound impact on weight loss. The reason that these drugs are so effective is due to their ability to stimulate cells within our gut to produce the hormone GLP-1, which is essentially a signal to your body that you are in a "fed state". This signal is detected by the pancreas, causing the release of insulin and the disposal of blood glucose (which is why the drug was initially meant to treat type 2 diabetes, due to the impact on blood glucose specifically). GLP-1 is also able to signal to the brain, which leads to a reduction in gastric emptying, and the slowing of digestion (which is one of the reasons people feel full so quickly on these medications)... The problem with these drugs, however, is the large proportion of people who experience significant side effects (mainly nausea and GI related distress, along with the potential to lose significant muscle mass). The side effect profiles are included in the clinical trial data (SURMOUNT, SURPASS, or SUSTAIN trials). What if I said you can have the same impact on GLP-1, but WITHOUT the drug and therefore without the side effects?!! Well guess what! YOU CAN!.. All you have to do is take care of your gut!! There are many strains and species of healthy bacteria lining our gut, and when we feed them dietary fiber (beans, vegetables, lentils, nuts, seeds, etc), they produce various short-chain fatty acids (butyrate, propionate, acetate). Those then go on to stimulate the gut to produce GLP-1!.. Which has the exact same effect that these pharmaceutical companies are going after!! Simply promoting a healthy gut microbiome with dietary fiber will result in an increase in GLP-1 secretion, and improved metabolic health. Here is a study exactly that (PMID: 29590046). Interested in learning more about the gut, and how it plays a role in our overall health? Tune in to the Kickback Science episode where we talk all about gut health: https://bit.ly/45jpJdf #gut #health #GLP1 #weightloss #metabolism #nutrition #fitness #science #research

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