PMID-36247927 – Mazdutide Phase 1b High-Dose Obesity Trial
Ji L, Gao L, Jiang H, et al. Safety and efficacy of a GLP-1 and glucagon receptor dual agonist mazdutide (IBI362) 9 mg and 10 mg in Chinese adults with overweight or obesity: A randomised, placebo-controlled, multiple-ascending-dose phase 1b trial. Diabetes Obes Metab. 2023;25(6):1512-1521.
Quick Reference
| Property | Value |
|---|---|
| PMID | 36247927 |
| DOI | 10.1111/dom.14900 |
| Year | 2023 |
| Journal | Diabetes, Obesity and Metabolism |
| Study Type | RCT (Phase 1b, randomized, placebo-controlled, multiple-ascending-dose) |
| Evidence Level | II |
| Sample | n=36 Chinese adults with overweight or obesity |
| Peptide(s) Studied | Mazdutide |
Key Findings
- Mean percent change from baseline to week 12 in body weight was -11.7% for mazdutide 9 mg and -1.8% for placebo
- Mazdutide 10 mg cohort showed comparable weight loss results
- High-dose mazdutide (9-10 mg) was well tolerated with an acceptable safety profile
- Most common adverse events were gastrointestinal (nausea, vomiting, diarrhea), consistent with GLP-1 class effects
- The study supported dose escalation beyond the 6 mg tested in earlier Phase 1 cohorts
Study Design
Randomized, double-blind, placebo-controlled, multiple-ascending-dose Phase 1b trial across five hospitals in China. Enrolled adults aged 18-75 years with BMI >=24 kg/m2 (with hyperphagia or obesity-related comorbidity) or BMI >=28 kg/m2. Two dose cohorts (9 mg and 10 mg) with 12-week treatment period. Subcutaneous once-weekly dosing with dose-escalation scheme.
Limitations
- Small sample size (n=36 total across both cohorts)
- Chinese population only — generalizability to other ethnic groups uncertain
- Short treatment duration (12 weeks)
- No active comparator arm (e.g., semaglutide)
Clinical Relevance
This Phase 1b study established that higher doses of mazdutide (9-10 mg) produce significant weight loss (~12%) in just 12 weeks while maintaining an acceptable safety profile. The results supported progression to Phase 2/3 dose-ranging studies and positioned mazdutide as a competitive dual GLP-1/glucagon agonist alongside survodutide.
Related
#research #RCT #mazdutide #evidence-level-II #metabolic