Incretin / GLP-1
Phase 3 Trials
Retatrutide
Also known as: LY3437943, triple agonist, GGG agonist
Triple agonist of the GIP, GLP-1 and glucagon receptors. Studied in metabolic research.
Research overview
Retatrutide (development code LY3437943) is a single synthetic peptide, developed by Eli Lilly, that activates three hormone receptors: the GIP, GLP-1 and glucagon receptors. In cell studies it is more active at the GIP receptor than at the other two, and in obese mice the glucagon receptor activity raised energy expenditure (Coskun et al., Cell Metab 2022). Phase 1 and phase 2 trials followed, including a randomised placebo-controlled phase 2 trial in 338 adults with obesity (Jastreboff et al., NEJM 2023). Randomised placebo-controlled phase 3 trials have since been published in people with type 2 diabetes and in adults with obesity, with and without type 2 diabetes, with 537 to 2,339 participants and lasting up to 80 weeks (Jastreboff et al., NEJM 2026). Gastrointestinal effects were the most common side effects, and one phase 3 trial reported low blood pressure and altered skin sensation (dysaesthesia) more often than with placebo.
Retatrutide is an investigational drug and is not approved as a medicine in the UK, EU or US. Its safety over longer periods than these trials is not known. Supplied for laboratory research use only.
Mechanism of action
Retatrutide binds and activates three G-protein coupled receptors: the receptors for the gut hormones GIP and GLP-1, and the receptor for glucagon, a hormone made by the pancreas. In cell assays it is more active at the GIP receptor than at the GLP-1 and glucagon receptors, which it activates to a similar degree. In obese mice, the glucagon receptor activity raised energy expenditure, while the GIP and GLP-1 receptor activity lowered calorie intake (Coskun et al., 2022).