Endocrinology · USMLE Step 1 and Step 2

GLP-1 Agonists song

GLP-1 Agonists - Mechanism & Side Effects, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

GLP-1 Agonists

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Key points in this song10

GLP-1 agonists (e.g., semaglutide, liraglutide, exenatide) mimic incretin hormone GLP-1, stimulating glucose-dependent insulin secretion and suppressing glucagon — low hypoglycemia risk when used as monotherapy.
Mechanism includes slowing gastric emptying, increasing satiety via hypothalamic signaling, and reducing hepatic glucose output — leading to significant weight loss alongside glycemic control.
Liraglutide (Victoza) and semaglutide (Ozempic/Wegovy) have demonstrated cardiovascular outcome benefits (reduced MACE) in patients with established atherosclerotic cardiovascular disease, making them preferred agents in T2DM with CVD.
Semaglutide also reduces risk of major adverse cardiovascular events in overweight/obese patients without diabetes (SURMOUNT/SELECT trials), expanding indications beyond glycemic control.
GLP-1 agonists are first-line preferred agents in T2DM patients with obesity, ASCVD, or high CV risk — per ADA guidelines.
Classic side effects are GI: nausea, vomiting, diarrhea — most prominent with initiation; dose-escalation titration minimizes discontinuation.
Contraindicated in patients with personal or family history of medullary thyroid carcinoma (MTC) or MEN type 2 — due to C-cell tumor risk shown in rodent studies.
Associated with pancreatitis risk — discontinue if acute pancreatitis is suspected; use with caution in patients with history of pancreatitis.
Exenatide (Byetta) is renally cleared and contraindicated in severe renal impairment (eGFR <30); semaglutide and liraglutide are safer alternatives in chronic kidney disease.
Oral semaglutide (Rybelsus) must be taken fasting with ≤4 oz water 30 minutes before food — unique absorption requirement due to peptide degradation in gastric acid.