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Mazdutide 9 mg Produces 12.78% Mean Weight Loss at 24 Weeks in Chinese Adults with Obesity
In a phase 2 randomized controlled trial, Chinese adults with obesity who received once-weekly mazdutide 9 mg lost a mean of 12.78% of body weight over 24 weeks, compared with a mean gain of 1.80% in the placebo group — a treatment difference of approximately 14.6 percentage points (95% CI −18.00 to −11.16, p < 0.0001). These results extend the efficacy profile of mazdutide to its highest tested dose and reinforce the potential of dual glucagon and GLP-1 receptor agonism as a pharmacological approach to obesity in Asian populations.
What Was Studied
This trial investigated whether mazdutide at a dose of 9 mg — administered once weekly — could produce clinically meaningful reductions in body weight among Chinese adults with obesity who did not have diabetes, with the primary outcome being percentage change in body weight from baseline at 24 weeks. The study builds on earlier phase 2 data demonstrating efficacy of mazdutide at lower doses (4 mg and 6 mg), and sought to determine whether dose escalation to 9 mg yields additional benefit while remaining well tolerated.
How It Was Studied
This was a randomized, double-blind, placebo-controlled phase 2 trial (registered as NCT01904913) conducted in Chinese adults with a body mass index of 30 kg/m² or above who did not have diabetes. A total of 80 participants were enrolled and randomly assigned in a 3:1 ratio, with 60 receiving mazdutide 9 mg once weekly and 20 receiving placebo, over a treatment period of 24 weeks. Mazdutide is a dual agonist targeting both glucagon and glucagon-like peptide-1 (GLP-1) receptors, a mechanistic profile that distinguishes it from pure GLP-1 receptor agonists. The trial was sponsored by Innovent Biologics.
What Was Observed
- Substantial weight reduction with mazdutide 9 mg: Participants receiving mazdutide lost an average of 12.78% of body weight from baseline, while those on placebo gained an average of 1.80%, yielding a treatment difference of approximately 14.6 percentage points (95% CI −18.00 to −11.16, p < 0.0001). This represents a highly statistically significant and numerically large separation between active treatment and control.
- High proportion reaching a clinically meaningful weight loss threshold: More than four in five participants on mazdutide — 81.7% — achieved at least a 5% reduction in body weight by week 24, a threshold commonly used to define clinically meaningful obesity treatment response. No participant in the placebo group reached this threshold.
- Improvements in cardiometabolic risk factors: Mazdutide treatment was associated with greater improvements in cardiometabolic parameters compared with placebo, though specific values for individual biomarkers were not detailed in the abstract.
- Gastrointestinal adverse events were common but mostly mild: The most frequent side effects in the mazdutide group were nausea (50.0% vs. 0% with placebo), diarrhea (38.3% vs. 10.0%), and vomiting (36.7% vs. 10.0%), consistent with the known tolerability profile of incretin-based therapies. These events were predominantly mild to moderate in severity.
Why This Matters
These findings extend the dose-response evidence for mazdutide beyond the previously studied 4 mg and 6 mg regimens, suggesting that further dose escalation can yield additional weight loss without a markedly different safety profile. The results are particularly relevant for understanding obesity pharmacotherapy in East Asian populations, who may have distinct metabolic risk profiles at lower absolute BMI thresholds. As a dual glucagon/GLP-1 receptor agonist, mazdutide’s mechanism may offer complementary metabolic benefits beyond those achieved by GLP-1 receptor agonism alone, supporting broader investigation of this drug class.
How to Read This Result
While the efficacy signal is strong and statistically compelling, the small sample size of 80 participants and the short 24-week follow-up period limit conclusions about long-term durability of weight loss and the safety profile over time; confirmation in larger phase 3 trials will be necessary before the clinical significance of these findings can be fully established.
Limitations
The abstract does not explicitly report study limitations.