DOI: 10.12688/f1000research.186694.1 ISSN: 2046-1402

Efficacy and Safety of Mazdutide for Type 2 Diabetes: a GRADE assessed systematic review and meta-analysis of randomized controlled trials

Affaf Mahmood, Noor Us Sehar, Aimen Farooq, Sajila Latif, Minahil Rasul, Shanza Abbasi, Amna Muhammad Ali, Eman Arshad, Mohammad Azeem Malik, Kawish Nenwani, Intzar Ahmed, Muhammad Sarmad, Rohma Khan, Sagar Kumar, Abdul Haseeb Hasan, Ahmad Hassan
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Background 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.

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