Efficacy and Safety of Mazdutide for Type 2 Diabetes: a GRADE assessed systematic review and meta-analysis of randomized controlled trials
Mazdutide shows promise in improving glycemic control and weight in adults with type 2 diabetes, but further research is needed to confirm these findings.
Where it sits
this study against the rest of the mazdutide (ibi362) corpusSummary and findings
Mazdutide was evaluated for its efficacy and safety in adults with type 2 diabetes mellitus (T2DM) compared to placebo. The study included three randomized controlled trials (RCTs) with a total of 613 participants. Significant reductions in HbA1c and body weight were observed.
Abstract
<h4>Background: </h4> Mazdutide, a dual glucagon-like peptide-1 (GLP-1) and glucagon receptor agonist, has shown promising metabolic benefits in randomized controlled trials (RCTs) of adults with type 2 diabetes mellitus (T2DM). However, its efficacy and safety have not been systematically synthesized. Objective To evaluate the efficacy and safety of mazdutide versus placebo in adults with T2DM. Methods A systematic review and meta-analysis of RCTs was conducted according to PRISMA 2020 guidelines. PubMed, Embase, Cochrane Library, and ScienceDirect were searched from inception through May 2026. Risk of bias was assessed using the Cochrane RoB 2 tool, and certainty of evidence was evaluated with the GRADE framework. Results Three RCTs involving 613 participants were included. Compared with placebo, mazdutide significantly reduced HbA1c (MD −1.53%; 95% CI −1.70 to −1.35), body weight (MD −4.22%; 95% CI −5.71 to −2.73), fasting plasma glucose, body mass index, waist circumference, blood pressure, and triglycerides. It also increased the likelihood of achieving HbA1c <7.0% (OR 9.04; 95% CI 3.05–26.76) and ≥5% weight loss (OR 10.61; 95% CI 3.72–30.29). Treatment-emergent and gastrointestinal adverse events were more frequent with mazdutide, while severe treatment-emergent and serious adverse events did not differ significantly between groups. Certainty of evidence ranged from very low to high. Conclusions Mazdutide significantly improves glycemic control, weight, and cardiometabolic risk factors in adults with T2DM, with a generally manageable short-term safety profile primarily characterized by gastrointestinal adverse events. Larger, longer-term multicenter RCTs are needed to confirm these findings.