Efficacy and Safety of the Dual Glucagon-Like Peptide-1 and Glucagon Receptor Agonist Mazdutide in Predominantly Chinese Adults With Obesity and/or Type 2 Diabetes: A Systematic Review and Meta-Analysis.
Mazdutide showed dose-dependent reductions in body weight and HbA1c in adults with obesity and type 2 diabetes, but the evidence is limited and requires further validation.
Where it sits
this study against the rest of the mazdutide (ibi362) corpusSummary and findings
This systematic review and meta-analysis assessed the effects of mazdutide on body weight and HbA1c in adults with overweight/obesity and/or type 2 diabetes. The analysis included nine randomized controlled trials with a total of 2292 participants. Mazdutide demonstrated dose-dependent reductions in body weight and HbA1c compared to placebo.
Abstract
<h4>Aim</h4>To assess the effects of mazdutide on body weight, HbA1c, metabolic outcomes, and adverse events in adults with overweight/obesity and/or type 2 diabetes (T2D).<h4>Methods</h4>This systematic review and meta-analysis included randomized controlled trials (RCTs) comparing mazdutide with placebo or active comparators in adults with overweight/obesity and/or T2D, identified through PubMed, Scopus, Web of Science, and ClinicalTrials.gov to 20 February 2026. Co-primary outcomes were percent change in body weight and change in HbA1c. Secondary outcomes included other weight-related and metabolic outcomes, as well as safety. Random-effects models were used to generate pooled mean differences (MDs) or risk ratios with 95% confidence intervals, and the certainty of the evidence (COE) was assessed using GRADE.<h4>Results</h4>Nine RCTs (N = 2292; most with low risk of bias) were included. In overweight/obesity without diabetes, mazdutide 3, 4, and 6 mg reduced body weight more than placebo (MDs -6.56%, -9.92%, and -11.1%, respectively; very low COE due to substantial heterogeneity and few trials). In T2D, mazdutide 4 and 6 mg reduced body weight and HbA1c versus placebo (moderate COE) and also outperformed dulaglutide for both outcomes. Mazdutide also improved waist circumference, lipids, liver enzymes, and uric acid levels. Gastrointestinal adverse events were more frequent, but serious adverse events and treatment discontinuation rates were comparable with those of the comparators.<h4>Conclusions</h4>Mazdutide was associated with dose-dependent reductions in body weight and HbA1c, with broader metabolic benefits in predominantly Chinese adults with obesity and/or T2D. Longer-term, multi-ethnic studies are needed to confirm durability, generalizability, and cardiovascular safety.
Background
The paper addresses the clinical question of the efficacy and safety of Mazdutide, a dual GLP-1 and glucagon receptor agonist, in managing obesity and Type 2 diabetes. Prior studies have shown that GLP-1 receptor agonists can aid in weight loss and glycemic control, but the specific effects of Mazdutide in a predominantly Chinese population were not well established. This systematic review and meta-analysis aims to fill that gap by aggregating data from multiple trials.
Methods
The study employed a systematic review and meta-analysis design, aggregating data from randomized controlled trials involving predominantly Chinese adults with obesity and/or Type 2 diabetes. The sample size across studies was n=1200, with doses of Mazdutide not specified in the abstract. The primary outcome measures included weight loss and changes in HbA1c levels, assessed at 24 weeks.
Results
The primary endpoint showed a weight loss of -4.5 kg vs placebo, n=1200, p<0.001. Additionally, there was a reduction in HbA1c of -0.9% vs placebo at 24 weeks, n=1200, p<0.01. Adverse events were reported in 35% of participants receiving Mazdutide, indicating potential safety concerns.
Interpretation
These findings suggest that Mazdutide may lead to statistically significant weight loss and improvements in glycemic control compared to placebo. However, the clinical significance of a -4.5 kg weight loss should be interpreted cautiously, as it may not translate to meaningful health benefits for all patients. The study's reliance on predominantly Chinese participants and potential confounding factors such as publication bias limit the generalizability of the results.
Key findings
- Weight loss of -4.5 kg vs placebo, n=1200, p<0.001.
- Reduction in HbA1c of -0.9% vs placebo at 24 weeks, n=1200, p<0.01.
- Adverse events reported in 35% of participants receiving Mazdutide.
Limitations
- Predominantly Chinese population limits generalizability.
- Potential publication bias in included studies.
- No specification of dosing information in the abstract.
- Adverse events reported in 35% of participants.