A physician prescribes semaglutide once weekly for a patient with type 2 diabetes and obesity. The primary mechanism by which semaglutide reduces appetite and body weight is:

• A Direct activation of GLP-1 receptors in the hypothalamic arcuate nucleus, POMC/CART neurons, and area postrema, reducing appetite ✓
• B Inhibition of dipeptidyl peptidase-4, prolonging endogenous GLP-1 action at hypothalamic satiety centres
• C Inhibition of gastric lipase reducing fat absorption and causing early satiety through fat malabsorption
• D Activation of PPAR-alpha receptors in adipose tissue promoting lipolysis and fatty acid oxidation

Explanation

Semaglutide is a GLP-1 receptor agonist (GLP-1 RA) that directly activates GLP-1 receptors in the hypothalamic arcuate nucleus (stimulating POMC/CART neurons) and area postrema/nucleus tractus solitarius, producing potent appetite suppression and reduced food intake. It also slows gastric emptying. DPP-4 inhibitors work indirectly by preventing GLP-1 degradation; orlistat inhibits gastric lipase; PPAR-alpha activation (fibrates) reduces triglycerides. GLP-1 RAs produce greater weight loss than DPP-4 inhibitors because supraphysiological GLP-1 levels are achieved.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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