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The role of antipsychotic agents in the development of diabetes mellitus

Nature Clinical Practice Endocrinology & Metabolism volume 5, pages 22–23 (2009)Cite this article

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Atypical or second-generation antipsychotic agents (SGAs) have improved efficacy and a reduced risk for extrapyramidal symptoms compared with older, first-generation (or typical) antipsychotic agents.1 Nonetheless, the use of SGAs has raised some concerns about potential adverse metabolic effects, such as an increased risk of diabetes mellitus, weight gain and dyslipidemia. Diabetes mellitus has been reported with all SGAs, the clinical pattern being consistent with type 2 disease.2 Theoretically, treatment-emergent diabetes mellitus could reflect either pre-existing undiagnosed disease, or increased susceptibility as a result of the underlying psychiatric disorder. Furthermore, a direct effect of the SGA, an indirect effect of weight gain, or an idiosyncratic, inherently unpredictable reaction in a susceptible individual might also explain the development of diabetes mellitus in patients receiving SGAs. In this Viewpoint, I discuss potential mechanisms of SGA-associated diabetes mellitus and strategies for effective management of affected individuals.

The fact that diabetes mellitus is reported in only a minority of patients exposed to SGAs weakens the case for a direct causal relationship. In terms of epidemiology, six criteria must be met to establish causality: validity of the observation method (e.g. randomized controlled trial versus case report); strength of the association; consistency; temporal coherence; biological plausibility; and strength of the dose–response relationship. These criteria have not been met with regard to SGA exposure and incident diabetes mellitus. This failure reflects a lack of data from randomized controlled trials, weak association, inconsistencies in the literature, an indeterminate temporal relationship (e.g. lack of baseline data in many cases), unclear biological mechanism(s), and an uncertain dose–response relationship.

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Acknowledgements

S Dagogo-Jack is supported in part by NIH Grants R01 DK067269 and MO1 RR00211.

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  1. Division of Endocrinology, Diabetes and Metabolism, University of Tennessee, Health Science Center, Suite 300A, 920 Madison Avenue, Memphis, TN 38163, USA sdj@utmem.edu

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  1. S Dagogo-Jack is a Professor of Medicine in the Division of Endocrinology, Diabetes and Metabolism at the University of Tennessee Health Science Center, Memphis, TN, USA.,

    Samuel Dagogo-Jack

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The author declared associations with the following companies: Eli Lilly (speakers bureau), GlaxoSmithKline (consultant and speakers bureau), Merck (consultant) and Pfizer (speakers bureau).

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Dagogo-Jack, S. The role of antipsychotic agents in the development of diabetes mellitus. Nat Rev Endocrinol 5, 22–23 (2009). https://doi.org/10.1038/ncpendmet1001

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