The Effects of Exercise Combined with Pharmacotherapy on Body Composition and Metabolic Parameters in Overweight/Obese Adults: A Meta-Analysis and Network Pharmacology Study

Objective: Overweight and obesity are major global health issues. Traditional interventions have limited efficacy, while pharmacological treatments are hindered by side effects and weight rebound. This study evaluates the effects of combined exercise and medication on body composition and metabolic health in overweight/obese adults, using network pharmacology to explore potential synergistic mechanisms. Methods: A systematic search of PubMed, EMBASE, Scopus, Web of Science, Medline, and Cochrane up to October 2025 identified 18 randomized controlled trials with 5,620 participants. Meta-analysis was performed using RevMan 5.4 and Stata 14. Outcomes included weight, BMI, body fat percentage, and metabolic markers. Network pharmacology was conducted using liraglutide and orlistat to identify shared targets and perform enrichment analysis. Results: Combined exercise and medication significantly reduced weight (MD = -2.49, 95% CI: -3.83, -1.14), BMI (MD = -0.79, 95% CI: -1.25, -0.34), and body fat percentage (MD = -1.97, 95% CI: -3.76, -0.18) compared to exercise alone. The combined intervention also significantly reduced systolic and diastolic blood pressure and triglycerides. However, compared to medication alone, it showed only reductions in weight and BMI, with no significant improvements in lean body mass, HDL, LDL, or fasting glucose. Network pharmacology revealed 109 obesity-related targets, including IL1B, STAT3, and SIRT1, involved in inflammation, lipid metabolism, and energy regulation. GO/KEGG analysis showed enrichment in fatty acid metabolism and AMPK signaling pathways. These pathways were highly consistent with metabolic adaptations induced by exercise, suggesting potential synergistic effects between exercise and medication in metabolic regulation. Conclusion: Combined exercise and medication significantly enhance weight loss in overweight/obese adults. Network pharmacology suggests that the IL1B-STAT3 inflammatory axis and SIRT1/CD36 lipid metabolism network may be central to the mechanisms. Future studies should explore the long-term efficacy and mechanistic specificity of different drug-exercise combinations.