The safety, tolerability, pharmacokinetics and pharmacodynamics of an optimized dual GLP-1/GIP receptor agonist (BGM0504) in healthy volunteers: A dose-escalation Phase I study.

Objective: Previous experiments have demonstrated that BGM0504, a GLP-1R/GIPR dual agonist drug by molecular dynamics-guided optimization, had enhanced agonistic activity compared to tirzepatide. This study aims to investigate its safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) in Chinese healthy volunteers.

Methods: A randomized, double-blind, placebo-controlled and dose-escalation Phase I study was conducted as follows: a single dose (2.5 mg) and once-weekly administration for 2 weeks to reach target doses (5, 10 and 15 mg) by titration.

Results: A total of 40 volunteers received at least one dose of BGM0504 or placebo. The PK profile of BGM0504 was investigated over a wide dose range and supported once-weekly administration. It was observed that C_max and AUC of BGM0504 were linearly proportional to the dose from 2.5-15 mg. The change in body weight (%) from baseline in BGM0504 groups was greater than that in the placebo group, with -3.24%, -6.26%, -7.09% and - 8.30% in 2.5, 5, 10 and 15 mg groups, respectively, indicating a certain dose correlation. Meanwhile, the potential roles of BGM0504 in glycaemic control were also observed. The most frequent adverse events reported were gastrointestinal (vomiting, nausea, decreased appetite, diarrhoea and abdominal distension).

Conclusion: BGM0504 was generally safe and well tolerated with favourable PK profile and potential role in weight loss was also confirmed. These findings support subsequent development of BGM0504 for type 2 diabetes mellitus (T2DM) and obesity.