Retatrutide

Retatrutide (CAS 2381089-83-2, Eli Lilly code LY3437943) is a unimolecular triple agonist of the GLP-1R, GIP-R and GCGR (glucagon receptor) receptors, composed of 39 amino acids with C20 diacid fatty acid acylation via γ-Glu-2×OEG linker on Lys17. It represents the third generation of incretin analogues after semaglutide (GLP-1 mono-agonist) and tirzepatide (GIP/GLP-1 dual), with strategic addition of GCGR agonism to potentiate energy expenditure and hepatic lipolysis.

Triple agonism mechanism. In addition to GLP-1R and GIP-R-mediated insulinotropic and satiety effects, glucagon receptor activation stimulates hepatic glycogenolysis and gluconeogenesis, increases brown adipose tissue thermogenesis, amplifies adipocyte lipolysis and raises resting energy expenditure by 8-12%. This triple coupling produces faster, more marked weight loss than dual agonists, with preferential visceral and hepatic fat reduction. The plasma half-life (~6 days) enables weekly administration.

Preliminary clinical data. The phase 2 trial published by Jastreboff reported mean weight loss of 24.2% at 48 weeks with the 12 mg/week dose (Jastreboff 2023 NEJM), surpassing tirzepatide. Phase III TRIUMPH-1 (simple obesity), TRIUMPH-2 (type 2 diabetes), TRIUMPH-3 (obesity with MASH) and TRIUMPH-4 (cardiovascular) studies are ongoing, with expected FDA submission 2026-2027.

Research use. Retatrutide is a tool of choice for preclinical studies combining diabetes, severe obesity, hepatic steatosis (MASH/MASLD) and cardio-metabolic dysfunction. DIO, db/db, ZDF, MCD and STAM rodent models are preferred to evaluate weight, glycaemic and hepatic effects. Lab Peptides France offers RUO retatrutide in 5mg, 10mg, 15mg, 20mg, 30mg and 40mg doses; five dosages were blind-tested by Janoshik (99.4 to 99.9% measured purity).