Bispecific GLP-1/GLP-2 agonism in advanced type 2 diabetes: preclinical characterization and a randomized, double-blind, placebo-controlled phase I trial - PubMed
6 hours ago
- #GLP-1/GLP-2 agonist
- #type 2 diabetes
- #phase I trial
- PG-102 is a bispecific Fc fusion protein targeting GLP-1 and GLP-2 receptors for advanced type 2 diabetes.
- In db/db mouse models, PG-102 achieved superior and sustained glycemic control compared to semaglutide or tirzepatide while preserving body weight.
- Mechanistic studies showed benefits driven by β-cell preservation and enhanced glucose uptake, not acute insulinotropic activity.
- Dual GLP-1R/GLP-2R engagement was required for efficacy, with PG-102 outperforming monospecific agonists or their combination.
- A phase I trial in overweight adults showed PG-102 was generally safe, with mild to moderate gastrointestinal adverse events and no serious events.