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Therapeutics

Retatrutide

DERetatrutid

Retatrutide (LY3437943) is an investigational once-weekly injectable peptide from Eli Lilly. It activates three receptors at once: the GLP-1 receptor (GLP-1R), the GIP receptor (GIPR), and the glucagon receptor (GCGR). Each one does a different job. GLP-1R curbs your appetite and slows your stomach emptying. GIPR boosts glucose-driven insulin release and makes fat tissue more responsive to GLP-1. GCGR raises your resting energy burn, through liver fat oxidation and (in animals) brown-fat heat production. That third action is missing from dual drugs like tirzepatide. The phase 2 obesity trial (Jastreboff et al., NEJM 2023) found a mean 24.2% weight loss at 48 weeks on 12 mg. About half of participants lost more than 25%, and liver fat fell by a mean of 82.4% at 24 weeks. A parallel phase 2 trial in type 2 diabetes (Rosenstock et al., Lancet 2023) showed bigger HbA1c and weight drops than placebo and dulaglutide 1.5 mg. Phase 3 TRIUMPH-1 topline data (May 2026) reported 28.3% mean weight loss at 80 weeks, on 12 mg, in 2,339 adults with obesity but no diabetes. Retatrutide is still investigational. No regulator had approved it as of mid-2026, and its long-term cardiovascular outcomes are not yet established.

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