350. GLP-1 Agonists: Mechanisms to Applications with Dr. Dennis Bruemmer

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.











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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?