Study Links Antipsychotic Use to Rapid Rise in Youth Type 2 Diabetes

Antipsychotic initiation in children and adolescents was followed by a rapid and progressively worsening rise in pharmacologically treated type 2 diabetes (T2D), according to a study published in JAMA Network Open.¹

Using Dutch population registry data spanning 2006 to 2022, researchers tracked 89,991 youths aged 0 to 19 years for 5 years before and 5 years after their first antipsychotic dispensation. The design compared each individual with themselves over time, controlling for stable person-specific factors that have limited earlier research in this area.¹

Risk Climbed Steadily After Treatment Start

Before antipsychotic initiation, treated T2D prevalence stayed low and flat, ranging from 0.76 to 2.78 cases per 10,000 users across the 5 preinitiation years. That pattern changed sharply once treatment began, with the prevalence reaching 6.22 per 10,000 users in the initiation year and climbing to 14.58 per 10,000 users by year 5, a risk difference of 9.02 additional cases per 10,000 users compared with the year before initiation.¹

A formal test of preinitiation trends found no significant differences before treatment started (joint Wald P = .63), supporting the interpretation that the postinitiation increase reflected the treatment itself rather than a metabolic decline already underway.¹

Risk did not accumulate evenly across the population. By year 5, female patients showed a risk difference of 16.48 per 10,000 users compared with 5.50 per 10,000 users among males. Adolescents aged 13 to 19 years accumulated substantially more excess risk than children aged 7 to 12 years, with the gap widening from year 4 onward. Youths from below-median and above-median household income neighborhoods showed broadly similar increases, suggesting no strong socioeconomic gradient in this particular outcome.¹

Notably, elevated risk was not confined to long-term users. Youths whose antipsychotic exposure was limited to the initiation year still showed a persistently elevated risk difference of 6.62 per 10,000 users by year 5, though recurrent users experienced a steeper, continuously rising risk that reached 10.17 per 10,000 users over the same period. The authors wrote that this finding "suggests that early treatment-related metabolic changes may not fully resolve after discontinuation in susceptible youths."¹

Pharmacy Monitoring Gaps Persist

The Dutch findings echo a well-established literature connecting antipsychotics to elevated diabetes risk. A 2019 review in Current Diabetes Reports found that diabetes prevalence runs 2 to 3 times higher in people with severe mental illness than in the general population, with second-generation agents implicated through both weight gain and direct effects on insulin sensitivity and secretion.²

That review noted that antipsychotics appear to worsen insulin resistance independent of weight change and that some agents impair insulin secretion from pancreatic β cells through dopaminergic, serotonergic, and muscarinic receptor pathways.²

Separate mechanistic research from the University of Toronto's Department of Psychiatry adds a central nervous system dimension to this picture. Investigators there found that antipsychotics can block the brain's ability to sense circulating glucose and adjust body-wide glucose metabolism accordingly, identifying this as a possible pathway by which the drugs raise diabetes risk independent of peripheral effects.³

Despite consistent evidence of risk, guideline-recommended metabolic monitoring in youths prescribed antipsychotics remains inconsistent in routine practice. The Dutch study's authors pointed to record reviews showing that more than half of children received no laboratory monitoring during antipsychotic follow-up and called for structured monitoring from the point of treatment initiation, paired with early lifestyle interventions such as dietetic referral and physical activity promotion.¹

This is an area where pharmacists can play a defined role. A 2023 commentary in the International Journal of Clinical Pharmacy outlined 3 contributions pharmacists can make to antipsychotic management, such as supporting shared decision-making through counseling on medications and adverse effects, closer integration within multidisciplinary care teams, and reducing unnecessary antipsychotic polypharmacy, which compounds metabolic and other risks. The commentary noted that pharmacists are often more accessible to patients than prescribing psychiatrists and are well positioned to reinforce metabolic screening and answer questions about side effects between formal appointments.⁴

Study Limitations

The Dutch study's authors acknowledged that their outcome measure—pharmacologically treated T2D—likely undercounts total diabetes cases, since it would miss undiagnosed or lifestyle-managed disease. They also could not distinguish between antipsychotic classes or individual agents, despite prior research indicating that risk varies meaningfully across drugs such as olanzapine, clozapine, and aripiprazole.^1,2

The authors called for structured metabolic monitoring and early preventive strategies to be implemented from the start of antipsychotic treatment in young people.¹

REFERENCES

1. Gangapersad RN, García-Gómez P, Koch BCP, Moghani V, Dierckx B. Antipsychotic Exposure and Pharmacologically Treated Type 2 Diabetes in Dutch Youths. JAMA Netw Open. 2026;9(7):e2625377. Published 2026 Jul 1. doi:10.1001/jamanetworkopen.2026.25377

2. Holt RIG. Association Between Antipsychotic Medication Use and Diabetes. Curr Diab Rep. 2019;19(10):96. Published 2019 Sep 2. doi:10.1007/s11892-019-1220-8

3. Gane B. Antipsychotics impair the brain's ability to regulate blood sugar. Department of Psychiatry, University of Toronto. January 24, 2023. Accessed August 3, 2026. https://psychiatry.utoronto.ca/news/antipsychotics-impair-brains-ability-regulate-blood-sugar

3. Howe J, Lindsey L. The role of pharmacists in supporting service users to optimise antipsychotic medication. Int J Clin Pharm. 2023;45(5):1293-1298. doi:10.1007/s11096-023-01630-9