Phase 1b trial of oral GLP-1 agonist HDM1002 shows weight reduction in Chinese adults with overweight/obesity

This phase 1b randomized controlled trial evaluated the safety, pharmacokinetics, and pharmacodynamics of multiple ascending doses of oral HDM1002, a small-molecule GLP-1 receptor agonist, in Chinese adults (aged 18-60 years) with a BMI between 24.0 and 36.0 kg/m² and without diabetes. Participants were randomized to receive HDM1002 at doses of 50 mg QD, 100 mg QD, 200 mg QD, 100 mg BID, or 400 mg QD, or placebo, for 28 days. The primary outcome was safety, assessed by treatment-emergent adverse events (TEAEs), vital signs, and laboratory parameters.

Regarding weight effects, the HDM1002 groups showed greater least squares mean reductions from baseline compared to placebo. The placebo group had a reduction of 1.6 kg, while the 200 mg QD group showed a 6.1 kg reduction, the 100 mg BID group a 4.4 kg reduction, and the 400 mg QD group a 4.3 kg reduction. No significant effect on glycemia was observed with HDM1002 compared to placebo. Pharmacokinetic analyses indicated generally dose-proportional exposure.

Safety data showed TEAEs in 60% of the placebo group and between 70% and 100% of the HDM1002 groups, with all events reported as mild or moderate. Two participants discontinued HDM1002 due to TEAEs versus none in the placebo group. The study reported a manageable safety and tolerability profile. Key limitations include its phase 1b nature, small sample size (12 participants per cohort), short 28-day duration, and lack of reported statistical comparisons for weight outcomes. These preliminary results require validation in larger, longer-term efficacy and safety trials.