Retatrutide — Triple GLP-1/GIP/glucagon receptor agonist

TRIUMPH Phase 2 trial (NEJM, 2023): 12mg retatrutide achieved 24.2% weight reduction at 48 weeks — the highest weight loss ever recorded for any pharmacotherapy in a Phase 2 trial (surpassing tirzepatide's 22.5%). The glucagon component also produced significant reductions in liver fat (>50% reduction in hepatic steatosis). The key mechanistic advantage over tirzepatide is increased energy expenditure (thermogenesis) in addition to reduced intake. The main safety concern is glucagon-mediated tachycardia; mean HR increase of ~5-8 bpm at highest doses. If Phase 3 data replicates Phase 2 findings, retatrutide may set a new benchmark for pharmacological weight management.

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

Triple GLP-1/GIP/glucagon receptor agonist

آلية العمل

Retatrutide is the first-in-class triple incretin agonist, simultaneously activating GLP-1, GIP, and glucagon receptors. The glucagon component critically distinguishes it from tirzepatide (dual GIP/GLP-1 only): hepatic glucagon receptor activation drives direct fat oxidation, increases energy expenditure through brown adipose tissue thermogenesis, and reduces hepatic steatosis independent of caloric restriction. GLP-1 receptor activation: appetite suppression, gastric emptying delay. GIP receptor activation: enhanced insulin sensitivity, reduced GLP-1 side effects. Glucagon receptor activation: fat oxidation, thermogenesis, direct lipolysis. The combination produces greater weight loss than any currently approved pharmacotherapy by simultaneously reducing intake AND increasing expenditure.

الوضع التنظيمي

Investigational — Phase 3 TRIUMPH trials ongoing (2024-2026)

مستوى الأدلة

Moderate — Phase 2 completed (n=338, TRIUMPH trial); Phase 3 ongoing