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, 12 (7), e0182088

The Risk of New-Onset Diabetes in Antidepressant Users - A Systematic Review and Meta-Analysis


The Risk of New-Onset Diabetes in Antidepressant Users - A Systematic Review and Meta-Analysis

Virginio Salvi et al. PLoS One.


Background: Antidepressant Drugs (ADs) are among the most commonly prescribed medications in developed countries. The available epidemiological evidence suggests an association between AD use and higher risk of developing type 2 diabetes mellitus. However, some methodological issues make the interpretation of these results difficult. Moreover, very recent studies provided conflicting results. Given the high prevalence of both diabetes and AD use in many countries, clarifying whether this association is causal is of extreme relevance for the public health. The aim of the present study is to provide an up-to-date evaluation of the evidence in support of a causal role of ADs in inducing diabetes.

Methods and findings: A systematic literature search was conducted to identify relevant studies in MEDLINE (PubMed), PsycINFO, and International Pharmaceutical Abstracts (IPA) through 31st December 2016. Only studies assessing the incidence of new-onset diabetes in subjects treated with ADs were included. Results were pooled using a random-effects meta-analysis. Moreover, we extensively reviewed the role of the different sources of bias that have been proposed to explain the association between AD and diabetes. Twenty studies met the inclusion criteria. In the meta-analysis, the association between AD use and diabetes was still evident after the inclusion of the recent negative studies [pooled relative risk = 1.27, 95% confidence interval (CI), 1.19-1.35; p<0.001]. None of the biases proposed by previous authors seemed able to fully explain the observed association.

Conclusions: This updated meta-analysis confirms the association between AD use and incident diabetes. It still remains a matter of debate whether single ADs exert a different effect on the risk of diabetes. Given the possible heterogeneity, we suggest that a classification of ADs according to their pharmacological profiles could be useful in better elucidating the nature of this association.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.


Fig 1
Fig 1. PRISMA Flow-Diagram of the systematic review.
Form: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group (2009). Preferred Reporting items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med 6(7): e1000097. doi:10.1371/journal.pmed1000097. For more information, visit
Fig 2
Fig 2. Random effects meta-analysis of the association between use of ADs and incidence of diabetes.

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Grant support

The study was partially supported by the University of Eastern Piedmont. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. There was no additional external funding received for this study.