Objective This systematic review and meta-analysis evaluated the efficacy, acceptability, and tolerability of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in individuals with severe mental illness (SMI). Methods PubMed, Embase, the Cochrane Library, Google Scholar, and ClinicalTrials.gov were searched on December 1, 2025, for randomized controlled trials (RCTs) of GLP-1RAs in participants with SMI. Primary outcomes were weight reduction, glycated hemoglobin (HbA1c) reduction, all-cause dropouts, and adverse-effect dropouts. Mean differences (MDs) and risk ratios (RRs) were estimated using a frequentist random-effects model. Results Included were 10 RCTs (N = 665) of exenatide, liraglutide, and semaglutide. Participants were those with schizophrenia, schizophrenia-spectrum disorders, or bipolar disorder with cardiometabolic risk. Compared with placebo/usual care, GLP-1RAs significantly reduced weight (MD = −6.17 kg, 95% CI: −9.10 to −3.25, I 2 = 91.8%, 9 trials) and HbA1c (MD = −0.31%, 95% CI: −0.40 to −0.22, I 2 = 51.3%, 8 trials). All-cause dropouts did not differ significantly between groups (RR = 0.98, 95% CI: 0.71 to 1.35, I 2 = 28.5%, 10 trials), nor did adverse-effect dropouts (RR = 0.99, 95% CI: 0.35 to 2.77, I 2 = 31.6%, 5 trials). Low-certainty evidence supports the tolerability and efficacy of GLP-1RAs for weight and HbA1c reduction. Moderate-certainty evidence also supports their acceptability. Conclusion Limited evidence suggests that GLP-1RAs may reduce body weight and slightly reduce HbA1c in individuals with SMI who have prediabetes or are overweight/obese. GLP-1RAs are likely acceptable and may be tolerated in this population.
Srisurapanont et al. (Sat,) studied this question.
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