Antipsychotic Exposure and Pharmacologically Treated Type 2 Diabetes in Dutch Youths

Antipsychotic medications are widely prescribed to children and adolescents worldwide, raising concerns about treatment-emergent type 2 diabetes (T2D). Previous studies have reported elevated T2D risks but have relied on between-person comparisons susceptible to unmeasured confounding and have not characterized risk trajectories around treatment initiation.

To determine the annual prevalence of pharmacologically treated T2D before and after antipsychotic initiation in Dutch youths.

This cohort study used data from Dutch population-based registers to track yearly pharmacologically treated T2D prevalence up to 5 years before and after antipsychotic initiation among youths aged 0 to 19 years initiating such medication. Using fixed-effects models, the event study design controlled for all stable, person-specific confounders that limit standard between-person comparisons. Data were collected from January 1, 2006, to December 31, 2022, and analyzed beginning in February 2025.

Antipsychotic initiation (first recorded dispensation).

The primary outcome was annual prevalence of pharmacologically treated T2D, defined as at least 1 dispensation of a noninsulin glucose-lowering medication within a given year. Annual risk differences (RDs) and relative risk changes were estimated using the year preceding antipsychotic initiation as the reference.

A total of 89 991 youths who were dispensed at least 1 antipsychotic prescription between 2006 and 2022 (median [IQR] age at antipsychotic initiation, 13.6 [9.8-16.7] years; 55 794 [62.0%] males) were included in the sample. In this cohort, pharmacologically treated T2D prevalence was stable before treatment and increased significantly after antipsychotic initiation. The RD increased from 2.47 (95% CI, 1.09-3.86) per 10 000 antipsychotic users in the initiation year to 9.02 (95% CI, 5.99-12.06) per 10 000 users by year 5. Females had greater absolute excess risk of T2D than males by year 5 (RD, 16.48 [95% CI, 8.95-24.00] per 10 000 users vs 5.50 [95% CI, 2.57-8.43] per 10 000 antipsychotic users). Adolescents aged 13 to 19 years had a larger long-term increase in risk than children aged 7 to 12 years (year-5 RD, 14.09 [95% CI, 8.19-19.98] per 10 000 users vs 5.47 [95% CI, 2.76-8.18] per 10 000 users). While recurrent users experienced greater, progressively increasing risk (RD, 10.17 [95% CI, 6.47-13.87] per 10 000 antipsychotic users by year 5), elevated risk of pharmacologically treated T2D persisted among youths using antipsychotics in the initiation year only.

In this within-individual cohort study, antipsychotic initiation in youths was associated with a rapid, sustained increase in treated T2D risk independent of underlying time-invariant factors. These findings indicate that even brief antipsychotic exposure is associated with a sustained metabolic vulnerability, underscoring the need for routine metabolic monitoring and preventive strategies from antipsychotic treatment initiation.