GLP-1 RAs and Metformin May Offer Different Clinical Benefits in antipsychotic-induced metabolic disturbances: Study

A new study published in the journal of BMC Medicine showed that GLP-1 receptor agonists and metformin could potentially provide distinct clinical advantages in managing metabolic complications induced by antipsychotic medications.

Managing metabolic issues caused by antipsychotic medication is a notable difficulty in the field of psychiatric healthcare. This research was conducted to consolidate randomized data and assess the comparative impacts of metformin and GLP-1 receptor agonists (GLP-1 RAs) on various metabolic factors and mental health symptoms in individuals experiencing antipsychotic-induced metabolic disturbances (AIMD) through a network meta-analysis approach.

Randomized controlled trials (RCTs) that were published until December 5, 2025, were found in PubMed, Embase, Cochrane Library, and Web of Science. The studies that met the criteria assessed the effectiveness of metformin or GLP-1 RAs for a minimum of 12 weeks alongside ongoing antipsychotic treatment. The Cochrane Risk of Bias 2.0 tool was used to evaluate bias risk.

A random-effects frequentist network meta-analysis was conducted using Stata 17.0 MP. Rankings of interventions were established by computing the surface under the cumulative ranking curve (SUCRA). Univariate network meta-regression was employed to investigate how study-level variables affected treatment outcomes. The quality of evidence was evaluated according to the CINeMA framework.

29 research studies involving 1,721 patients were part of the analysis. The average age across the studies was 36.2 years, with 47.7% of the participants being male, and the typical treatment period lasted for 16 weeks.

Semaglutide, when compared to control groups, led to decreases in body mass index (BMI) (mean difference = -3.55, 95% confidence interval: -4.27 to -2.84), waist circumference (WC) (mean difference = -6.34, 95% confidence interval: -8.17 to -4.51), glycated hemoglobin A1c (HbA1c) (mean difference = -0.44, 95% confidence interval: -0.53 to -0.35), and fasting blood glucose (FBG) (mean difference = -0.53, 95% confidence interval: -0.88 to -0.18).

Metformin was linked to decreases in indicators of lipid metabolism, such as total cholesterol (TC) and triglycerides (TG), and indicated a possible positive effect on psychiatric symptom scores (standardized mean difference = -0.31, 95% confidence interval: -0.55 to -0.06).

Overall, estimates from indirect network analysis indicate that these treatments could result in varied outcomes. GLP-1 RAs may offer advantages for weight and blood sugar levels, while metformin might be beneficial for cholesterol levels and mental health symptoms.

Reference:

Chen, Y.-X., Yang, Q.-W., Lin, M.-X., Sun, M.-H., Dong, Y.-Y., Yu, R.-D., Mao, D.-D., Zhao, Y., Zhang, L., Zhao, J.-X., Zhang, Y.-F., & Xu, J. (2026). Metformin and GLP-1 receptor agonists for antipsychotic-induced metabolic disturbances: a systematic review and network meta-analysis. BMC Medicine. https://doi.org/10.1186/s12916-026-05280-2