JAMA Psychiatry

Antipsychotic drugs linked to disrupted glucose regulation, independent of weight gain

August 29, 2025

Study details: This systematic review and meta-analysis included 127 blinded randomized trials comparing antipsychotic (AP) use to placebo or no intervention in patients with severe mental illness or healthy volunteers. The analysis evaluated changes in fasting glucose, insulin, HbA1c, and other glucose metabolism parameters, with subgroup and metaregression analyses accounting for diagnosis, AP type, treatment duration, and weight gain propensity.

Results: Across nearly 44,000 participants, AP use was significantly associated with:

• Increased fasting glucose: mean difference [MD], 0.72 mg/dL; 95% confidence interval (CI), 0.54-1.08; P<.001
• Insulin: MD, 1.94 μIU/mL; 95% CI, 1.28-2.61; P<.001
• HbA1c: MD, 0.04%; 95% CI, 0.02%-0.05%; P<.001
• Odds of hyperglycemia: odds ratio, 1.29; 95% CI, 1.04-1.59; P=.02

These effects were consistent across subgroups and independent of AP dose, treatment duration, or prior exposure. Notably, dysglycemia was also observed in healthy volunteers.

Clinical impact: Antipsychotic-induced glucose dysregulation occurs independently of weight gain and may affect all patient populations, including those without prior AP exposure. Early and ongoing metabolic monitoring is warranted for all patients on APs, regardless of diagnosis or treatment stage.

Source:

Smith ECC, et al. (2025, August 27). JAMA Psychiatry. Antipsychotic Drugs and Dysregulated Glucose Homeostasis: A Systematic Review and Meta-Analysis. https://pubmed.ncbi.nlm.nih.gov/40864439/