Efficacy and Safety of Mazdutide in Managing Overweight and Obesity Among Non-Diabetic Adults: A Meta-Analysis of Randomised Controlled Trials.
This meta-analysis pooled data from five randomised controlled trials to evaluate the efficacy and safety of mazdutide — a dual GLP-1 and glucagon receptor agonist — for weight management in non-diabetic adults with overweight or obesity. Searches were conducted across Cochrane Library, PubMed, Google Scholar, and ClinicalTrials.gov, and analyses were performed using random-effects models in RevMan 5.4. The pooled results reported by the study authors indicate that mazdutide was associated with significant reductions in percentage body weight (mean difference –12.42%), absolute body weight (–9.76 kg), and waist circumference (–7.98 cm) compared with control conditions. Secondary cardiometabolic outcomes — including systolic blood pressure (–7.68 mmHg), total cholesterol (–0.57 mmol/L), and LDL cholesterol (–0.37 mmol/L) — also showed reductions. Adverse events were slightly more frequent in the mazdutide groups (RR = 1.12), described as mild to moderate. A dose-wise meta-regression suggested a significant dose-dependent relationship. The authors acknowledge that findings are constrained by the small number of included trials (n = 5), which limits the robustness and generalisability of conclusions.
Why this grade: Although the study synthesises data from RCTs in humans — the highest study design tier — the evidence is graded moderate rather than strong due to the small number of included trials (only five RCTs), which the authors themselves identify as a key limitation affecting precision and generalisability.
Background Mazdutide, a dual GLP-1 and glucagon receptor agonist, shows promise for weight loss and glycaemic control. This study evaluates its efficacy in non-diabetic patients with obesity. Methodology A search of Cochrane Library, PubMed, Google Scholar and clinicaltrials.gov identified randomised controlled trials (RCTs) of mazdutide in adults (≥ 18 years) with obesity. Meta-analysis was performed using RevMan 5.4 with random-effect models. Results Five RCTs were included. Mazdutide significantly reduced percentage body weight (MD = -12.42%, 95% CI: -16.15% to -8.68%), absolute body weight (MD = -9.76 kg, 95% CI: -13.15 to -6.37 kg) and waist circumference (MD = -7.98 cm, 95% CI: -10.24 to -5.72 cm). Systolic blood pressure (MD = -7.68 mmHg), total cholesterol (MD = -0.57 mmol/L) and LDL (MD = -0.37 mmol/L) also decreased. Adverse events were slightly increased (RR = 1.12). Dose-wise meta-regression showed significant effects (β = -0.99, 95% CI: -1.81 to -0.16; p = 0.0187). Conclusion Mazdutide effectively reduces weight, waist circumference and blood pressure but may cause mild to moderate adverse events. Findings are limited by the small number of RCTs.
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