semaglutide — GLP-1 receptor agonist (weekly, acylated)

Semaglutide represents the most significant advance in obesity pharmacotherapy in decades. The SELECT trial's cardiovascular outcome data (2023) elevated semaglutide from a weight loss drug to a cardiovascular medicine — the 20% MACE reduction in non-diabetic obese patients is comparable to statin benefit. Key prescribing nuance: the titration protocol is critical — rushing the dose escalation dramatically increases GI intolerance and discontinuation. Muscle loss during rapid weight loss is a genuine concern — high protein intake (1.2-1.6g/kg/day) and resistance training are strongly recommended adjuncts. The 'Ozempic face' (facial volume loss) is a cosmetic concern from rapid weight loss, not a direct drug effect. Supply shortages have led to widespread compounding pharmacy use — compounded semaglutide safety/potency is unregulated.

نظرة عامة

هذه الصفحة جزء من مكتبة المركّبات المُصنَّفة بالأدلة في Hormonaly. جميع الادعاءات السريرية مرتبطة بمصادر علمية مُحكَّمة عبر خط أنابيب التحقق المزدوج للاستشهادات.

فئة المركّب

GLP-1 receptor agonist (weekly, acylated)

آلية العمل

Human GLP-1 analog with 94% amino acid sequence homology to native GLP-1. Modified at position 8 (Aib substitution — DPP-4 resistance) and lysine 26 (C18 fatty diacid chain via linker — albumin binding enabling once-weekly dosing; t½ ~7 days). Mechanism: (1) GLP-1R agonism in pancreatic β-cells → glucose-dependent insulin secretion; (2) Suppresses glucagon (α-cells); (3) Hypothalamic GLP-1R activation → satiety, reduced appetite, decreased caloric intake; (4) Delays gastric emptying; (5) Direct cardiovascular effects via GLP-1R in cardiac tissue — reduces inflammation, improves endothelial function. The SUSTAIN-6 and SELECT trials demonstrated CV mortality reduction. STEP trials: Wegovy (2.4mg weekly) achieves 15-17% mean body weight loss at 68 weeks vs ~2.4% placebo.

الوضع التنظيمي

FDA approved — Ozempic (SC, T2DM) 2017; Rybelsus (oral, T2DM) 2019; Wegovy (SC 2.4mg, obesity) 2021; semaglutide CVI (Ozempic, CV risk reduction) 2023

مستوى الأدلة

High — Multiple FDA-approved indications with Phase 3 SUSTAIN (T2DM), STEP (obesity), and SELECT (CV outcomes) trial programs. SELECT (2023, n=17,604) showed 20% reduction in major adverse cardiovascular events in obese/overweight adults without diabetes — first weight loss drug with proven CV mortality benefit.