Semaglutide, a GLP-1 receptor agonist, causes significantly greater weight loss than older GLP-1RAs. This is partly explained by its:
- A Higher potency at hypothalamic GLP-1 receptors in the arcuate nucleus reducing appetite
- B Additional GIP receptor agonism compared to liraglutide, potentiating hypothalamic satiety signalling
- C Longer half-life (once weekly) and higher receptor occupancy permitting greater CNS appetite suppression over time ✓
- D Blockade of ghrelin receptor in the stomach, reducing hunger signalling
Correct answer: C. Longer half-life (once weekly) and higher receptor occupancy permitting greater CNS appetite suppression over time
Explanation
Semaglutide's enhanced weight-loss effect is attributed to its superior pharmacokinetics: a C18 fatty-diacid moiety with a hydrophilic spacer links it to albumin, extending its half-life to ~1 week (vs liraglutide's 13 hours). Sustained, high-level GLP-1 receptor occupancy in the hypothalamus (arcuate and paraventricular nuclei) and in the hindbrain (area postrema) more durably reduces appetite and food intake. Tirzepatide is the dual GLP-1/GIP receptor co-agonist; semaglutide is a selective GLP-1RA.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.