Citations 1
Efficacy and safety of semaglutide versus placebo for people with schizophrenia spectrum disorders with obesity or early-stage metabolic abnormalities: A systematic review and meta-analysis of randomized controlled studies
Rasul, Minahil , Hassan, Ahmad , Rehman, Ubaid ur , Sarmad, Muhammad, Farooq, Abdullah Shahid, Khalil, Huzaifa, Jahangir, Muhammad Asad , Bashir, Muhammad Kashif , Cheema, Umaima , Amir, Maaz , Malik, Mohammad Azeem , Hasan, Abdul Haseeb , Tahir, Ramisha, Farooq, Abdullah Shahid , Abideen, Zain Ul
Therapeutic Advances in Psychopharmacology | August 18, 2026 | Volume: 16 | Issue: No issue available | Pages: No page available
Background Individuals with schizophrenia spectrum disorders are at increased risk of cardiometabolic complications, largely due to antipsychotic-associated metabolic effects. Effective management strategies remain limited. Semaglutide, a glucagon-like peptide-1 receptor agonist, has shown metabolic benefits in the general population, but its role in this population remains unclear. Objective To evaluate the efficacy and safety of semaglutide compared with placebo in individuals with schizophrenia spectrum disorders receiving antipsychotic therapy and experiencing metabolic abnormalities. Design Systematic review and meta-analysis of randomized controlled trials. Data Sources and Methods: A systematic review and meta-analysis was conducted following PRISMA guidelines. PubMed, Cochrane Library, Embase, and ScienceDirect were searched from inception to February 2026. Randomized controlled trials comparing semaglutide with placebo were included. The longest follow-up time point from each study was used for pooled analysis. Mean differences (MD) and odds ratios (OR) with 95% confidence intervals (CIs) were calculated using RevMan 5.4. The certainty of evidence for critical outcomes was assessed using the GRADE framework. Results Three randomized controlled trials (n = 258) were included. Semaglutide was associated with reductions in body weight (MD: -11.01 kg), BMI (MD: -3.63 kg/m 2 ), and waist circumference (MD: -6.33 cm). Improvements were also observed in body composition. No significant differences were found in lipid or glycemic parameters except HbA1c which showed a significant reduction. Psychiatric outcomes remained unchanged. Gastrointestinal adverse particularly nausea and vomiting events were more frequent with semaglutide. Conclusion Semaglutide appears to improve anthropometric outcomes without worsening psychiatric symptoms in individuals receiving antipsychotic therapy. However, evidence is limited, and larger, long-term trials are required. According to the GRADE framework, the certainty of evidence ranged from moderate for key anthropometric and safety outcomes to low or very low for several metabolic and psychiatric outcomes, highlighting the need for larger, long-term randomized trials.