A diabetic patient with HbA1c 9.2% and significant obesity is started on semaglutide. Which mechanism correctly explains its glucose-lowering and weight-reducing effect?

• A It activates PPAR-gamma receptors in adipocytes, enhancing insulin sensitivity and reducing appetite via leptin upregulation
• B It inhibits DPP-4 enzyme, prolonging endogenous GLP-1 half-life, and directly blocks ghrelin receptors to reduce appetite
• C It is a GLP-1 receptor agonist that augments glucose-dependent insulin secretion, inhibits glucagon, delays gastric emptying, and acts centrally to reduce appetite ✓
• D It blocks alpha-2 receptors on beta cells, increasing glucose-stimulated insulin secretion and reducing hypothalamic neuropeptide Y

Explanation

Semaglutide is a long-acting GLP-1 receptor agonist. GLP-1 receptor stimulation in the pancreatic beta cells augments glucose-stimulated insulin secretion (glucose-dependent, thus avoiding fasting hypoglycaemia) and suppresses glucagon from alpha cells. Delayed gastric emptying reduces postprandial glucose excursions. Central GLP-1 receptor activation in the hypothalamus and brainstem reduces appetite and energy intake, producing significant weight loss. DPP-4 inhibitors differ by preserving endogenous incretin — they do not directly activate the receptor.

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

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