Effectiveness, Safety and Pharmacokinetics of BGM0504, a Dual GLP-1/GIP Receptor Agonist, in Chinese Adults With Overweight or Obesity Without Diabetes: A Phase 2 Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial.

AIMS: To evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and efficacy of the dual GLP-1R/GIPR agonist BGM0504 in Chinese adults with overweight or obesity without diabetes. MATERIALS AND METHODS: In this randomized, double-blind, placebo-controlled, parallel-group phase 2 trial, 120 participants were assigned (1:1:1:1) to receive once-weekly subcutaneous injections of BGM0504 5 mg, 10 mg, 15 mg, or placebo for 24 weeks. The primary endpoint was percentage change in body weight from baseline to week 24. Key secondary endpoints included absolute body weight change, waist circumference, and the proportions of participants achieving prespecified weight-loss targets. Safety was assessed using adverse events, laboratory tests, and vital signs. The trial was registered with the Chinese National Medical Products Administration (CTR20233198) and ClinicalTrials.gov (NCT06973681). RESULTS: Mean percentage changes in body weight from baseline to week 24 were -10.68%, -16.07%, -18.33%, and 0.13% with BGM0504 5 mg, 10 mg, 15 mg, and placebo, respectively; all BGM0504 doses were significantly superior to placebo (all p < 0.0001). Mean reductions in waist circumference were -8.88 cm, -12.71 cm, -14.38 cm, and -1.03 cm, respectively (all p < 0.001 vs. placebo). The proportions of participants achieving clinically meaningful weight loss increased in a dose-dependent manner across BGM0504 groups versus placebo (all p < 0.001). PK analyses showed an approximately linear dose-exposure relationship across the evaluated dose range. TEAEs occurred in 96.7%, 93.5%, 100.0%, and 86.7% of participants in the BGM0504 5 mg, 10 mg, 15 mg, and placebo groups, respectively, and drug-related adverse events occurred in 53.3%, 80.6%, 93.1%, and 40.0%. The most common selected TEAEs were gastrointestinal, including nausea, diarrhoea, and vomiting. One serious adverse event occurred in the 10 mg group and no TEAEs led to trial withdrawal. CONCLUSIONS: Once-weekly BGM0504 was associated with substantial dose-dependent weight loss and acceptable tolerability in Chinese adults with overweight or obesity without diabetes, supporting further clinical development.