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

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Background Type 2 diabetes mellitus (T2DM) remains a major global health burden. Although glucagon-like peptide-1 receptor agonists (GLP-1RAs) such as dulaglutide improve glycemic control and promote weight loss, many patients do not achieve optimal metabolic targets. Mazdutide, a dual GLP-1 and glucagon receptor agonist, may provide greater efficacy. This systematic review and meta-analysis compared the efficacy and safety of mazdutide versus dulaglutide in adults with T2DM. Methods PubMed, Embase, Cochrane Library, and ScienceDirect were searched through May 2026 for randomized controlled trials comparing mazdutide with dulaglutide. Outcomes included glycemic control, weight loss, cardiometabolic parameters, and safety. Data were pooled using fixed- or random-effects models according to heterogeneity, and certainty of evidence was assessed using the GRADE framework. Results Three RCTs involving 990 participants (mazdutide, n=683; dulaglutide, n=307) were included. Mazdutide significantly reduced HbA1c (mean difference [MD] −0.25%; 95% CI −0.38 to −0.12; p=0.0002) and body weight (MD −3.74%; 95% CI −5.29 to −2.19; p<0.00001) compared with dulaglutide. It also increased the likelihood of achieving ≥5% and ≥10% weight loss and improved blood pressure and triglyceride levels. No significant differences were observed in fasting plasma glucose or HbA1c target achievement (<7%). Treatment-emergent adverse events were more frequent with mazdutide (OR 1.69; 95% CI 1.16–2.45), mainly due to gastrointestinal effects, while serious adverse events were similar between groups. GRADE certainty was high for primary efficacy outcomes, moderate for most safety outcomes, and low to very low for infrequent adverse events. Conclusions Mazdutide demonstrated superior glycemic control, weight reduction, and cardiometabolic benefits compared with dulaglutide, with more frequent but generally mild gastrointestinal adverse events. These findings support mazdutide as a promising treatment option for T2DM, although longer-term comparative studies are needed.

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