Semaglutide and Liraglutide Significantly Reduce Antipsychotic-Induced Weight Gain in Schizophrenia Patients

Patients with schizophrenia spectrum disorders (SSDs) frequently experience significant antipsychotic-induced weight gain (AIWG), particularly with highly effective agents like clozapine and olanzapine. This adverse effect contributes substantially to cardiometabolic morbidity, including type 2 diabetes and cardiovascular disease, and often impairs treatment adherence. Current management strategies for AIWG lack a strong consensus, highlighting an urgent need for effective pharmacological interventions to mitigate these severe metabolic disturbances and improve long-term patient outcomes.

This systematic review and frequentist random-effects network meta-analysis evaluated pharmacological interventions for weight reduction in antipsychotic-treated patients with SSDs. Researchers systematically searched Ovid MEDLINE, Embase, PsycINFO, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, and ICTRP up to December 5, 2025. They included 95 randomized clinical trials examining 39 individual pharmacological interventions, with a pooled N=5898 participants. The primary outcome was change in body weight, comparing pharmacological agents against placebo or standard care, with certainty of evidence assessed using the CINeMA tool.

The network meta-analysis identified several pharmacological interventions significantly associated with weight reduction. Semaglutide demonstrated the most substantial effect, with a mean difference (MD) of -10.98 kg (95% CI, -13.33 to -8.62; k=3 studies; moderate certainty). Liraglutide also showed significant efficacy, resulting in an MD of -5.43 kg (95% CI, -8.54 to -2.33; k=2 studies; moderate certainty). Topiramate reduced weight by an MD of -3.95 kg (95% CI, -5.89 to -2.02; k=5 studies; moderate certainty), while metformin yielded an MD of -3.86 kg (95% CI, -5.89 to -1.83; k=15 studies; moderate certainty). These findings provide robust evidence for the efficacy of GLP-1 receptor agonists and other agents in managing AIWG. > Semaglutide led to the most pronounced weight reduction, averaging -10.98 kg, offering a significant therapeutic option for antipsychotic-induced weight gain.