UBT251, a novel triple GLP-1, GIP, and glucagon receptor agonist, in adults with overweight or obesity: A multicenter, randomized phase 2 trial.

UBT251 is a novel triple agonist targeting glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, and glucagon receptors. In this multicenter, randomized, double-blind, placebo-controlled phase 2 trial, 205 adults with overweight or obesity (59.0% women; aged 18-61 years; without type 2 diabetes) received once-weekly UBT251 at 2 mg, 4 mg (initial dose 0.5 mg or 1 mg), or 6 mg, or placebo for 24 weeks. For the primary efficacy endpoint, least-squares mean percentage changes in body weight at week 24 were -19.7% to -13.6% with UBT251 vs. -2.0% with placebo; placebo-adjusted differences were -17.7% (95% confidence interval [CI], -20.8% to -14.6%) to -11.5% (95% CI, -14.1% to -9.0%; all p < 0.001). UBT251 improved waist circumference, body mass index, blood pressure, lipid profiles, and glycemic parameters. The most frequent adverse events were mild-to-moderate gastrointestinal symptoms. UBT251 produced weight reduction with cardiometabolic improvements and an acceptable safety profile, supporting phase 3 evaluation. This study was registered at China Drug Trials Registry (CTR20250288) and ClinicalTrials.gov (NCT07177469).