TOPLINE:

The use of antipsychotic drugs was associated with dysregulated glucose control (homeostasis) independent of weight gain compared with use of placebo, with increased levels of fasting glucose, insulin, and A1c, a new meta-analysis showed.

METHODOLOGY:

• In a systematic review of 163 studies published between 1970 and 2024, 127 randomized clinical trials had meta-analyzable data on glucose homeostasis parameters.
• Nearly 29,000 participants were treated with antipsychotics, and more than 15,000 received placebo. The most diagnosed conditions were schizophrenia spectrum disorder (56 studies) and bipolar disorder (48 studies).
• Overall, 15 different antipsychotics were represented in the analysis; 86% of the studies involved adults, and the others involved children and/or adolescents.
• Primary outcomes were changes in fasting glucose, fasting insulin, and A1c levels following antipsychotic treatment. Secondary outcomes included changes in other glucose metabolism parameters, such as hyperglycemia and insulin resistance.

TAKEAWAY:

• Compared to placebo use, antipsychotics use was associated with significantly increased levels of fasting glucose (mean difference, 0.72 mg/dL; P < .001), fasting insulin (mean difference, 1.94 µIU/mL; P < .001), and A1c (mean difference, 0.04%; P < .001) and an increased risk for hyperglycemia (odds ratio [OR], 1.29; P = .02) but not for insulin resistance.
• Type and dose of antipsychotic used, diagnosis, age, concomitant medication use, and previous exposure to antipsychotics did not consistently affect the risk for abnormal glucose level (dysglycemia).
• Further analyses showed that fasting glucose and insulin levels were not significantly associated with weight gain.

IN PRACTICE:

“AP [antipsychotic]-induced dysglycemia puts a population already vulnerable to metabolic dysregulation at even greater risk for long-term health consequences; the current findings should motivate development of new APs with fewer cardiometabolic adverse effects and/or more effective metabolic interventions,” the investigators wrote.

SOURCE:

The study was led by Margaret K. Hahn, MD, PhD, Centre for Addiction and Mental Health, Toronto, Ontario, Canada. It was published online on August 27 in JAMA Psychiatry.

LIMITATIONS:

A limited number of trials for certain drugs and outcomes were included, and the use of study‐level pooled analyses may have masked individual antipsychotic effects and a potential aggregation bias. Most trials lacked detailed prior exposure data, had short median durations insufficient for measuring reliable A1c changes, and rarely used gold‐standard insulin‐sensitivity measures. Additionally, potential ceiling effects among participants and heterogeneity in drug dosing and follow up limited interpretation, and the statistically significant absolute increases in glucose may not have been clinically meaningful.

DISCLOSURES:

Several investigators reported having financial or other ties with pharmaceutical and biotech companies. Full details are provided in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.