Objective: To evaluate the efficacy and safety of semaglutide combined with metformin in treating type 2 diabetes mellitus (T2DM) patients who are overweight or obese. Methods: We conducted a comprehensive search across multiple databases including Wanfang, CNKI, Chinese Biomedical Literature, VIP, Embase, PubMed, Cochrane Library, and Web of Science. Studies were screened to include randomized controlled trials (RCTs) comparing semaglutide combined with metformin versus metformin alone in T2DM patients with obesity or who are overweight. Primary outcomes included glycemic efficacy and body mass index (BMI). Secondary endpoints included pancreatic function, blood lipids, and incidence of adverse effects. Pooled and sensitivity analyses were performed, and risk of bias was assessed. Results: Ten studies met the inclusion criteria, all involving oral semaglutide. Compared with placebo, semaglutide with metformin significantly reduced fasting blood glucose (SMD: -0.94; 95% CI: -1.53 to -0.35) and 2-hour postprandial glucose (SMD: -0.97; 95% CI: -1.44 to -1.50; P0.05). Conclusion: Treatment with semaglutide combined with metformin significantly improved glycemic control, insulin resistance, weight, BMI, and lipid profiles in patients with T2DM who are overweight or obese.
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