Juan Pablo Frias, M.D.
National Research Institute, Los Angeles
Lead author, Lancet Phase 2 GLP-3R T2D trial (2023).
GLP-3R is a triple-receptor agonist (GIP / GLP-1 / glucagon) currently in Phase 2/3 clinical trials for obesity and type 2 diabetes, developed by Eli Lilly. It has demonstrated up to ~24% body weight reduction at 48 weeks in the highest dose groups — surpassing earlier dual-agonist drugs like tirzepatide.
Mechanism of action
- Simultaneous agonism of GLP-1, GIP, and glucagon receptors — a class-first triple action.
- GLP-1 activation contributes to glucose-dependent insulin signaling and appetite regulation.
- GIP receptor engagement modulates adipose tissue handling and insulin sensitivity.
- Glucagon receptor activity increases energy expenditure and hepatic lipid oxidation.
Research highlights
- Lancet Phase 2 (2023): up to 24.2% mean weight reduction at the 12 mg dose at 48 weeks.
- Phase 2 type 2 diabetes trial demonstrated improvements in HbA1c and fasting glucose alongside body weight changes.
- PMC systematic review and meta-analysis aggregating randomized controlled trials supports a consistent dose-dependent signal.
