Novel GLP-1 agonist BGM0504 significantly reduced HbA1c up to 2.48% in Chinese adults with T2DM.

Type 2 Diabetes Mellitus (T2DM) remains a global health challenge, characterized by chronic hyperglycemia and progressive pancreatic beta-cell dysfunction. Despite advancements, many patients struggle to achieve optimal glycemic control, leading to severe microvascular and macrovascular complications. Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as highly effective therapeutics, offering robust glycemic control, weight loss, and cardiovascular benefits. However, there's a continuous need for novel agents with improved efficacy, safety, or pharmacokinetic profiles, particularly for diverse patient populations like those in China, where specific genetic and lifestyle factors may influence treatment response.

This multicenter, randomized, double-blind, placebo- and active-controlled Phase II trial enrolled 64 Chinese adults with Type 2 Diabetes. Participants were assigned to receive BGM0504 5 mg (n=12), 10 mg (n=12), 15 mg (n=12), placebo (n=12), or semaglutide 1 mg (n=16). All treatments were administered once weekly via subcutaneous (SC) injection for 12 weeks. The primary endpoint was the change in HbA1c from baseline, with secondary endpoints including fasting plasma glucose (FPG), 2-hour postprandial glucose (2h PG), and body weight. Safety and tolerability were monitored through adverse events, laboratory tests, and vital signs.

At Week 12, BGM0504 demonstrated a dose-dependent reduction in HbA1c from baseline. The mean HbA1c changes were -1.72% for the 5 mg dose, -1.94% for the 10 mg dose, and -2.48% for the 15 mg dose. For comparison, semaglutide 1 mg showed a -1.43% change, while placebo resulted in a 0.28% increase. The treatment differences versus placebo (LSM) for BGM0504 ranged from -1.82% to -2.56% (all p<0.05), indicating statistically significant improvements. The proportion of participants achieving HbA1c <6.5% or <7.0% also increased in a dose-dependent manner. BGM0504 also showed significant reductions in FPG, 2h PG, and body weight (all p<0.05).

Notably, the 15 mg dose of BGM0504 demonstrated superior body weight reduction compared to semaglutide 1 mg.

Pharmacokinetic analysis confirmed a linear exposure-response relationship, and all doses of BGM0504 were well tolerated, with most adverse events being mild.