Study wrapper · #843
Glucagon-like peptide-1 receptor agonists for weight management in mental illness: a network meta-analysis.
Editor's note
This network meta-analysis of nine RCTs (595 participants, mostly schizophrenia-spectrum) examines GLP-1 receptor agonists for weight in people with serious mental illness — a group at high cardiometabolic risk, often from antipsychotic-related weight gain. Semaglutide is directly evaluated and posts the largest weight effect versus control (standardized mean difference −2.10), with associated reductions in BMI, waist circumference, fasting glucose, and HbA1c, alongside the expected higher gastrointestinal side effects (nausea, vomiting, constipation). Both semaglutide and liraglutide beat control on weight. The authors are appropriately restrained: they call semaglutide's top ranking uncertain because the networks are sparse, heterogeneity is substantial, and evidence is largely indirect. With only 595 participants across nine trials, confidence intervals are wide and the semaglutide arm rests on limited data. Read this as an encouraging but preliminary signal that semaglutide can address weight in a high-need psychiatric population, not as settled comparative evidence. Larger dedicated trials are needed.
Plain-language abstract
People with serious mental illness such as schizophrenia often gain significant weight, partly from their medications, raising their risk of diabetes and heart disease. This analysis combined nine randomized trials (595 people total, most with schizophrenia-spectrum conditions) to see how well GLP-1 receptor agonist drugs — including semaglutide, liraglutide, and exenatide — help with weight and related measures in this group. Semaglutide showed the largest weight reduction compared with placebo and was also linked to lower BMI, smaller waist size, and better blood-sugar markers. As expected for this drug class, it caused more nausea, vomiting, and constipation. Liraglutide also reduced weight compared with placebo. The researchers cautioned that semaglutide's apparent top ranking is uncertain because there were few trials, the studies varied a lot from one another, and much of the comparison relied on indirect evidence rather than head-to-head testing. In short, the findings suggest these drugs — semaglutide in particular — may help manage weight in people with serious mental illness, but the evidence is still limited and larger studies are needed.