GLP-1 receptor agonists (liraglutide, semaglutide) produce weight loss as a major benefit. The mechanism of their weight-reducing effect is:
- A Activation of GLP-1 receptors in the hypothalamus and brainstem, reducing appetite and promoting satiety, plus delayed gastric emptying ✓
- B Inhibition of lipase enzyme, reducing dietary fat absorption
- C Increase in basal metabolic rate through thyroid hormone-like activity
- D Blockade of cannabinoid CB1 receptors in the gut, reducing hunger signals
Explanation
GLP-1 receptors are expressed not only on pancreatic beta cells but also extensively in the hypothalamus (particularly the arcuate nucleus and nucleus tractus solitarius) and vagal afferents. Activation of these central GLP-1 receptors reduces food intake by increasing satiety signals (POMC neurons activated) and decreasing appetite neuropeptides (NPY/AgRP). Additionally, GLP-1 agonists delay gastric emptying, slowing nutrient absorption and prolonging the sense of fullness. The weight loss effect is dose-dependent and is largely independent of the glucoincretin (insulin-stimulating) effect. Semaglutide at higher doses (2.4 mg weekly SC) is now approved specifically for obesity management.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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