Glucagon is a 29-amino-acid hormone from the pancreas that raises blood sugar by signaling the liver to release glucose. It also increases energy use, which is why drug developers have added glucagon-receptor activity to newer obesity drugs.
Lilly's retatrutide acts on the GLP-1, GIP, and glucagon receptors. In the TRANSCEND-T2D-2 trial it produced about twice the weight loss of Ozempic over 80 weeks in adults with type 2 diabetes, and Lilly plans to file for FDA approval in the first quarter of 2027. Researchers are also studying the hormone itself: an October 2026 Copenhagen study in 15 healthy adults found that a glucagon infusion lowered insulin clearance without significantly changing insulin secretion.
Stories here cover glucagon-based drugs and the biology behind them. See #retatrutide, #triple-agonist, and #survodutide.
Researchers at Bispebjerg and Frederiksberg Hospital gave 15 healthy adults a four-hour intravenous glucagon infusion on one day and a glucose infusion meant to match the resulting blood sugar on another, reporting in the Journal of the Endocrine Society. Insulin secretion, the primary endpoint, did not differ significantly between days (P = 0.12), but a post hoc analysis found insulin clearance was lower during glucagon at both high and normal blood sugar (P = 0.0003). The glucose matching was incomplete, and the result bears on drugs such as retatrutide that add glucagon-receptor activity.
STAT reported June 6 that new safety data presented at ADA showed seven of 403 retatrutide-treated patients experienced arrhythmias and three had major cardiovascular events, compared with none in the placebo group. The signal had been a watch item ahead of ADA because retatrutide adds glucagon-receptor activity to GLP-1 and GIP, raising heart-rate and energy-expenditure mechanisms that have not appeared in the same way for semaglutide or tirzepatide. Lilly's larger TRIUMPH-OUTCOMES cardiovascular trial reads out in 2027.
Richard DiMarchi and Matthias Tschöp — whose work enabled Eli Lilly's Zepbound and the modern GLP-1 class — published a peer-reviewed draft paper arguing that targeting GIP and glucagon receptors alone, without GLP-1, may deliver comparable weight loss without the nausea and vomiting that plague current therapies. The experimental molecule, backed by BlueWater Biosciences, challenges the central dogma of obesity drug design. Results are preclinical and must still translate to humans.
MetaVia dosed the first patient in a higher-dose Phase 1 study of DA-1726, its GLP-1 and glucagon dual agonist for obesity treatment, marking continued advancement in next-gen weight loss drugs.