1745-P - Long-Term Safety and Efficacy of Once-Weekly Dosage of 2.4 mg Semaglutide for Weight Loss in Patients with and without Diabetes—An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials

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Author Block: MIAN MUHAMMAD SALMAN ASLAM, WANIA U. REHMAN, QURAT UL AIN M. MUHAMMAD, MUHAMMAD TALHA SHAUKAT, MUHAMMAD HASSNAIN NASRULLAH, MUHAMMAD HASSAN, FATIMA SAEED, MUHAMMAD A. TARIQ, Ann Arbor, MI, Rawalpindi, Pakistan, Boston, MA, Lahore, Pakistan
Disclosure Block: M.Aslam: None. W.U.Rehman: None. Q.M.Muhammad: None. M.Shaukat: None. M.Nasrullah: None. M.Hassan: None. F.Saeed: None. M.A.Tariq: None.

Introduction and Objective: Obesity is a multifaceted health crisis necessitating a nuanced understanding to direct evidence-based therapeutic strategies. Glucagon-like peptide-1 receptor agonists (GLP1RAs) such as semaglutide have shown encouraging yet contradictory outcomes. This study aims to evaluate the long-term efficacy and safety of once-weekly 2.4 mg semaglutide for weight loss in patients with and without diabetes.
Methods: A systematic search was conducted in MEDLINE (via PubMed), Cochrane Library, Google Scholar, and ClinicalTrials.gov up to December 31, 2024, for relevant randomized controlled trials (RCTs) comparing semaglutide versus placebo. The protocol was registered on PROSPERO (ID: CRD42024532538). Meta-analysis was performed using R statistical software to calculate mean differences (MD), risk ratios (RR), and corresponding 95% confidence intervals (CI).
Results: Twelve RCTs with 23,600 participants (semaglutide: 12,492; placebo: 11,108) were included. Semaglutide significantly reduced body weight compared to placebo, with a mean percentage reduction of -7.91% and an absolute reduction of -10.40 kg (p < 0.01). Higher proportions of patients in the semaglutide group achieved weight loss thresholds of ≥10%, ≥15%, and ≥20% (p < 0.01). Waist circumference, fasting plasma glucose, and lipid profiles improved (p < 0.01). Adverse events, primarily gastrointestinal, were more common with semaglutide (RR = 1.56; p < 0.01), contributing to higher discontinuation rates (RR = 4.67; p < 0.01).
Conclusion: Semaglutide demonstrates robust efficacy in achieving significant weight loss and improving metabolic parameters in patients with and without diabetes. However, its tolerability remains a challenge, warranting further research to optimize safety.