Once-Weekly Mazdutide in Chinese Adults with Obesity or Overweight
Ji L, Jiang H, Bi Y, Li X, Shi L, Liu J, Yang G, Zhao L, +2 more
New England Journal of Medicine (2025) · n=610
GLORY-1 reported mean body-weight reductions of -12.55% on mazdutide 6 mg versus +0.45% on placebo at 32 weeks in Chinese adults with obesity — the first Phase 3 readout for a Chinese-developed incretin in a population the global obesity trials have under-recruited.
GLORY-1 is the pivotal Phase 3 trial for mazdutide, Innovent Biologics' glucagon and GLP-1 receptor dual agonist (IBI362), developed under license from Eli Lilly's discovery-stage OXM-3 molecule. Ji and colleagues randomized 610 Chinese adults with obesity (BMI ≥28) or overweight (BMI 24.0–27.9 with at least one weight-related comorbidity) in a 1:1:1 ratio to once-weekly subcutaneous mazdutide 4 mg, mazdutide 6 mg, or matching placebo for 48 weeks, with a primary efficacy analysis at week 32. The trial was conducted across multiple Chinese clinical sites and was sponsored by Innovent Biologics.
At week 32, the 6-mg mazdutide arm achieved a mean body-weight reduction of -12.55% versus +0.45% on placebo. By week 48, the 6-mg arm showed -14.01% versus +0.30% on placebo. Co-primary endpoint analysis included the proportion of patients achieving ≥5% weight reduction, which favored both mazdutide doses substantially over placebo. Adverse events were dominated by gastrointestinal complaints (nausea, vomiting, diarrhea) of mild-to-moderate severity, concentrated during dose escalation. Discontinuation for adverse events was low across all arms (1.5%, 0.5%, and 1.0%). Cardiometabolic risk factors improved across active doses consistent with the broader incretin class.
GLORY-1 occupies a specific niche in the obesity-pharmacotherapy literature: the first Phase 3 readout for a Chinese-developed incretin in a Chinese population. The body-weight magnitude — 14% at the 6-mg dose at week 48 — is competitive with the GLP-1-only class (semaglutide 2.4 mg in Chinese subpopulations has produced ~10–12% at similar durations) but below the GIP / GLP-1 (tirzepatide) and triple-agonist (retatrutide) signals seen in predominantly Western populations. Whether the population difference, the molecule's pharmacology, or both account for the cross-trial spread is not resolvable from the GLORY-1 data alone. The trial's regulatory significance is high: mazdutide received Chinese NMPA approval for obesity on the basis of GLORY-1, making it the first dual glucagon / GLP-1 agonist approved anywhere in the world.
Generalizability of GLORY-1 to non-Chinese populations is the question the trial does not answer. Asian populations, and Chinese populations specifically, tend to develop metabolic disease at lower BMI thresholds than European populations — which is why the trial used BMI ≥24 for the overweight stratum rather than the ≥27 threshold typical of Western trials. Whether mazdutide's effect profile in a Chinese cohort transfers cleanly to higher-BMI Western populations is being addressed in follow-on programs but has not read out.
The 32-week primary endpoint and 48-week extension are appropriate for an obesity Phase 3 program by current standards but short relative to the chronic-therapy positioning the field has adopted. Long-term durability, post-treatment regain dynamics, and cardiovascular outcomes data for mazdutide are addressed in the Phase 3 SURPASS-equivalent program rather than in this paper.
Industry sponsorship by Innovent Biologics is disclosed; the trial was conducted in collaboration with multiple Chinese tertiary care centers. The active comparator question — mazdutide versus semaglutide 2.4 mg or tirzepatide head-to-head — is partially addressed in companion Phase 3 trials but the global cross-comparison literature on glucagon-containing co-agonists is still being built. Mazdutide's availability outside China remains constrained by Innovent's commercial geography; Lilly retains rights in the US and EU but has prioritized tirzepatide and retatrutide development in those markets. As of 2026, mazdutide is approved and marketed in China but not in the US, EU, or UK.
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