Effectiveness and safety of semaglutide in overweight/obese adults with or without type 2 diabetes: A systematic review and meta-analysis

Background: The objective of the study was to systematically evaluate the efficacy and safety of semaglutide in overweight or obese adults with or without type 2 diabetes. Materials and Methods: The study, registered with PROSPERO (CRD42023450979), was designed as a systematic review and meta-analysis. Using a combination of subject matter and free words, a comprehensive search of Embase, PubMed, and Cochrane Library databases was performed to identify randomized controlled trials of semaglutide in overweight or obese adults with or without Type 2 diabetes mellitus from January 1, 2020, to July 14, 2023. The primary outcomes were the changes in body weight and adverse drug reaction (ADR). Random or fixed effects models were used in meta-analysis, pooling data as relative risks (RRs) or mean difference (MD) with 95% confidence intervals (CIs). Cochrane Collaboration's Risk of Bias tool was used to assess quality. Meta-analysis was performed using RevMan 5.3.Results: A total of 2490 publications were retrieved. Fifteen publications were finally included, totaling 6984 overweight or obese adult patients. Meta-analysis showed that compared with the control group, the semaglutide group was reduced more significantly in body weight (MD = -7.49, 95% CI [-9.92, -5.07], P < 0.001), body mass index (MD = -3.35, 95% CI [-4.79, -1.92], P < 0.001), waist circumference (MD = -7.26, 95% CI [-9.94, -4.58], P < 0.001), as well as glycosylated hemoglobin (RR = -0.66, 95% CI [-1.07, -0.25], P = 0.002), fasting blood glucose values (RR = -4.81, 95% CI [-7.03, -2.60], P < 0.001), and systolic blood pressure (RR = -3.37, 95% CI [-5.32, -1.42], P < 0.001), and the proportion of patients who lost > 5%, 10%, 15%, and 20% of their overall body weight, respectively (RR = 3.19, 95% CI [1.89, 5.36], P < 0.001), (RR = 4.74, 95% CI [2.78, 8.11], P < 0.001), (RR = 6.17, 95% CI [3.88, 9.82], P < 0.001), and (RR = 9.14, 95% CI [6.05, 13.80], P < 0.001) were also superior to the control group. Regarding safety, the incidence of total ADR in the semaglutide group was close to the placebo group. Still, gastrointestinal adverse effects such as nausea, vomiting, abdominal pain, and diarrhea were higher than those in the control group.Conclusion: Semaglutide can effectively lose weight in overweight or obese adults with or without diabetes, potentially providing cardiovascular benefits; however, gastrointestinal adverse should be closely monitored.