Antipsychotic drugs tied to glucose homeostasis disruption

Treatment with antipsychotics may lead to a significant glucose homeostasis dysregulation, regardless of exposure time, dose, diagnosis, and weight gain propensity, according to systematic review and meta-analysis.

Researchers searched multiple online databases for randomized controlled trials in which changes in glucose homeostasis-related parameters in patients with severe mental illness or healthy volunteers were examined in relation to antipsychotic use vs placebo or no intervention.

The search yielded 22,773 unique citations, of which 163 met the inclusion criteria and 127 were included in the meta-analysis. Most of the trials involved patients with either schizophrenia spectrum disorder (SSD) (n=76) or bipolar disorder (BD) I and II (n=57), while the few ones enrolled patients with major depressive disorder (MDD) (n=16) and healthy volunteers (n=14). Study duration ranged between a single dose to 104 weeks (mean 10.7 weeks). In total, there were 35,952 patients treated with antipsychotics and 19,010 patients who received placebo.

Pooled data showed that compared with placebo, antipsychotics was associated with marked elevations in fasting glucose (mean difference [MD], 0.72 mg/dL, 95 percent confidence interval [CI], 0.54–1.08; p<0.001), fasting insulin (MD, 1.94 μIU/mL, 95 percent CI, 1.28–2.61; p<0.001), and glycated haemoglobin (MD, 0.04 percent, 95 percent CI, 0.02–0.05; p<0.001).

Antipsychotic use also increased the odds of hyperglycaemia (odds ratio, 1.29, 95 percent CI, 1.04–1.59; p=0.02).

These findings were consistent with those in healthy volunteers.

Subgroup analyses indicated that antipsychotic type, diagnosis, age, concomitant medication use, and previous antipsychotic did not modify the association between antipsychotics and dysglycaemia risk. Further analyses showed that antipsychotic-associated dysregulations in glucose homeostasis were independent of study length and dose.

The present data highlight the importance of ongoing metabolic monitoring of patients on antipsychotics and administering potential treatment for the associated glucose homeostasis dysregulations.