PubMed1 Apr 2026·Obesity (Silver Spring, Md.)● 5/10i HDM1002 in Chinese Adults With Overweight/Obesity: A Randomized, Placebo-Controlled, Ascending-Dose Phase 1b Study.
Xu H, Hu W, Zhao L, Tu W, Shen L et al.
HDM1002, a small-molecule GLP-1 receptor agonist, achieved 6.1 kg weight loss at 200 mg daily versus 1.6 kg with placebo over 28 days in Chinese adults with overweight or obesity. Phase 1b randomized controlled trial, 60 participants across five dose cohorts. This represents the first clinical data for an oral small-molecule GLP-1 agonist showing meaningful weight loss, potentially offering an alternative to injectable peptides in obesity treatment. All participants in higher dose groups experienced adverse events, with two discontinuations.
Strategic signal
An oral small-molecule GLP-1 agonist achieving meaningful weight loss positions this asset as potential competition to Novo's oral semaglutide, which requires complex formulation and dosing restrictions. If HDM1002 maintains efficacy in longer studies without the absorption challenges plaguing oral semaglutide, it could offer manufacturing cost advantages and simpler dosing. The China-first development suggests targeting regulatory arbitrage, similar to how Chinese companies advanced COVID antivirals ahead of Western approvals.
GLP-1Weight loss
Original Abstract
OBJECTIVE: HDM1002, a small-molecule agonist of glucagon-like peptide-1 receptors, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD). METHODS: Chinese participants (18-60 years) with BMI ≥ 24.0 kg/m2 to ≤ 36.0 kg/m2 without diabetes were enrolled and randomized 5:1 (12 per cohort) to receive HDM1002 or placebo orally for 28 days. Dose cohorts included 50 mg once daily (QD); 100 mg QD; 200 mg QD; 100 mg twice daily (BID); and 400 mg QD. Primary endpoint was safety, assessed by treatment-emergent adverse events (TEAEs), vital signs, physical examination, electrocardiogram, and laboratory parameters. Secondary endpoints were PK/PD analyses. RESULTS: TEAEs in 50/100/200 mg QD, 100 mg BID, and 400 mg QD HDM1002 groups were 80%, 70%, 100%, 90%, and 100%, respectively, and 60% in the placebo group, all mild/moderate. Two participants discontinued HDM1002 due to TEAEs versus none in the placebo group. Greater least squares mean reductions from baseline in body weight were among HDM1002 200 mg QD (-6.1 kg), 100 mg BID (-4.4 kg), and 400 mg QD (-4.3 kg) groups, compared with placebo (-1.6 kg). There was no significant effect on glycemia observed with HDM1002 compared to placebo. PK were generally doseproportional. CONCLUSIONS: HDM1002 demonstrated a manageable safety/tolerability profile. TRIAL REGISTRATION: CTR20233390.