Retatrutide

Also: LY3437943, GGG tri-agonist

Summary

Retatrutide is a synthetic peptide developed by Eli Lilly that acts on three hormone receptors at once: GLP-1, GIP and glucagon. It is an investigational drug in late-stage clinical trials for obesity and type 2 diabetes and is not yet licensed anywhere. Its long duration of action comes from a fatty-acid chain attached to the peptide.

What it targets

Retatrutide activates the GLP-1, GIP and glucagon receptors, which between them influence appetite, insulin release and energy expenditure. In a phase 2 trial substudy in adults with type 2 diabetes, it reduced total body fat mass measured by DXA compared with placebo and dulaglutide over 36 weeks, with gastrointestinal effects the most common adverse events. In diet-induced obese rats, combining it with cagrilintide lowered body weight and food intake more than either drug alone. A mouse study presented as a conference abstract reported reduced pancreatic tumour growth at a dose that did not cause weight loss; that finding has not been published as a full paper.

body weight and fat mass (phase 2, type 2 diabetes)combination with cagrilintide (rats)pancreatic cancer growth (mice, conference abstract)

Clinical Research

Effects of retatrutide on body composition in people with type 2 diabetes: a substudy of a phase 2, double-blind, parallel-group, placebo-controlled, randomised trial
Coskun T, Wu Q, Schloot NC, et al. (2025). The Lancet Diabetes & Endocrinology. human adults with type 2 diabetes, phase 2 substudy, n=189 enrolled (103 with paired DXA scans)
Cagrilintide and retatrutide combination therapy enhances weight loss and metabolic outcomes in obese male rats
Petersen J, Merrild C, Holm SK, et al. (2026). Nature Metabolism. animal diet-induced obese male rats
661 Retatrutide monotherapy matches the effectiveness of anti-PD-1 immunotherapy in a preclinical model of pancreatic cancer
Marathe SJ, Bohm MS, Powell Z, et al. (2025). Journal for ImmunoTherapy of Cancer (SITC 2025 abstract supplement). animal diet-induced obese male C57BL/6J mice with implanted pancreatic tumour cells, n=10 per group

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