Atypical Antipsychotics and Diabetes: Some Physiologic Links Emerging

Jeannette Y. Wick, RPh, MBA, FASCP
Published Online: Tuesday, July 10th, 2018
Patients on atypical antipsychotics have 3 to 5 times greater risk of type 2 diabetes than others. This is an association that clinicians have noted since the first of the atypicals was FDA approved, and patients struggle when diabetes develops. The association between schizophrenia and diabetes is convoluted. Researchers believe that both biologic and lifestyle factors contribute to this association.
A study in the American Journal of Physiology-Endocrinology and Metabolism examines the link between atypical antipsychotics and type 2 diabetes. Researchers have clinical evidence that glucose dysregulation developed even in the absence of weight gain.
Second generation (or atypical) antipsychotics include asenapine, aripiprazole, clozapine, iloperidone, lurasidone,olanzapine, paliperidone, quetiapine, risperidone, and ziprasidone. The main difference between typical and atypical antipsychotics is that atypical antipsychotics target both dopamine and serotonin, which decreases extrapyramidal symptoms that include spasms and movement disorders. Atypical antipsychotics are thought to be more effective and work faster than their typical counterparts.
Weight gain is a common side effect of atypical antipsychotics, which many people believe explains changes in glucose metabolism. Researchers believe that diabetes associated with atypical antipsychotics goes beyond weight gain, however.
Researchers have documented a link between diabetes and atypical antipsychotics in patients who did not gain weight by looking at case reports of diabetic ketoacidosis induced by second-generation antipsychotics. Looking at in-vivo studies on rodents, researchers found that peripheral insulin sensitivity decreases with atypical antipsychotic administration.
Although research has not established a direct link that shows dysregulation of hepatic insulin sensitivity in humans, clinicians should still be cautious. These researchers note that this difference may be due to differences in central and peripheral kinetics, and drug metabolism.
Patients often take atypical antipsychotics for conditions other than schizophrenia, and off-label for other psychiatric conditions. Routine follow-up and close monitoring of blood glucose and HbA1c levels may help catch type 2 diabetes early.


Kowalchuk C, Castellani L, Chintoh A, Remington G, Giacca A, Hahn M. Antipsychotics and glucose metabolism: how brain and body collide. Am J Physiol Endocrinol Metab. 2018 Jul 3. doi: 10.1152/ajpendo.00164.2018. [Epub ahead of print]

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