Semaglutide 2.4 mg for weight loss in overweight adolescents and adults without diabetes: an updated systematic review and meta-analysis of randomized controlled trials

Background: Obesity, a metabolic disorder, is a major contributor to morbidity and mortality worldwide [15]. Behavioral interventions alone often fail to achieve sustained weight loss [17, 18]. Thus, this systematic review and meta-analysis aims to determine the effect of semaglutide 2.4 mg for weight loss in overweight adolescents and adults without diabetes. Methodology: A comprehensive search was conducted across PubMed, Scopus, Web of Science, and randomized controlled trial (RCT) registries, with no time-frame limitation. A total of 593 research papers were retrieved; 12 met the inclusion criteria for systematic review, and 9 were included in the meta-analysis. RevMan version 5.3. was used, with statistical significance set at P < 0.05. Results: Once-weekly subcutaneous semaglutide 2.4 mg resulted in significant 10.8% reduction in body weight (95% CI −13.03 to −8.57), a 6.95 cm decrease in waist circumference (95% CI -7.18, -6.72), 3.61 mmHg reduction in systolic blood pressure (95% CI -4.00, -3.21), a 0.29% decrease in HbA1c (95% CI -0.31, -0.22) and a 36.21% reduction in CRP levels (95% CI -36.35, -36.06), compared to placebo. Gastrointestinal adverse events and treatment discontinuation were more frequent with semaglutide, while hypoglycemia or fatal events showed no significant differences. Conclusion: Semaglutide 2.4 mg is an effective pharmacologic option for weight reduction in adolescents and adults without diabetes, with significant metabolic benefits. Careful monitoring of gastrointestinal adverse effects remains essential.