Summary

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• This summary is based on the review of 39 systematic review(s)/meta-analysis(es). ^[1-37]
• Weight Loss: Semaglutide resulted in substantial weight reductions in overweight and obese adults, achieving up to -11.49% and -11.74 kg of weight loss compared to placebo. It significantly increased the likelihood of >5%, >10%, >15%, and >20% weight loss across populations, with consistent effectiveness observed in both diabetic and non-diabetic individuals.
• Cardiometabolic Benefits: Improvements were observed in glycosylated hemoglobin (HbA1c), fasting blood glucose, and systolic blood pressure. Additionally, semaglutide reduced major adverse cardiovascular events (MACE) and all-cause mortality, particularly in non-diabetic overweight or obese adults.
• Comparative Efficacy: Semaglutide generally induced greater weight loss compared to other glucagon-like peptide-1 receptor agonists (GLP-1RA) like liraglutide, dulaglutide, and exenatide. However, tirzepatide, a dual GLP-1 and Gastric inhibitory polypeptide (GIP) receptor agonist, demonstrated superior weight loss outcomes.
• Subgroup Effectiveness: In pediatric populations, semaglutide showed significant weight loss compared to placebo and other GLP-1RAs. Non-diabetic adults experienced slightly better weight loss outcomes than diabetic populations, reinforcing its efficacy across diverse groups.
• Semaglutide was associated with a higher incidence of gastrointestinal adverse effects, including nausea, vomiting, abdominal pain, and diarrhea, compared to placebo, with these effects being dose-dependent and a leading cause of treatment discontinuation.
• The risk of serious adverse events did not significantly differ from placebo, though specific issues such as gastrointestinal and hepatobiliary disorders, including acute pancreatitis and cholelithiasis, were reported. Discontinuation due to adverse events was more common with semaglutide than placebo.
• Compared to other GLP-1RAs, semaglutide had a similar or slightly higher incidence of gastrointestinal adverse effects, with liraglutide showing higher rates of nausea, vomiting, hypoglycemia, and injection-site reactions.
• Semaglutide demonstrated significant weight loss efficacy in obese or overweight non-diabetic adults and adolescents, with higher efficacy observed in non-diabetic adults; however, gastrointestinal adverse events were more common, particularly in pediatric populations, requiring careful monitoring. Additional subgroup benefits included cardiovascular risk reduction in non-diabetic adults and potential mitigation of psychotropic drug-related weight gain in adults with psychiatric conditions, with no significant variation in safety across ethnic, body mass index, or demographic subgroups.