Antidepressants Use and the Risk of Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis

Background: This study aimed at examining the effects of different antidepressants on the new onset of T2DM.

Methods: Systematic literature retrieval for cohort and case-control studies was conducted in PubMed, Embase, Web of Science, Cochrane library, Clinical Trials Register of the Cochrane Collaboration and CENTRAL published from January 2000 to October 2020. Pooled estimates were calculated and subgroup analyses were conducted by a fixed or random effects model according to the heterogeneity. Funnel plots and Egger's test were performed to evaluate publication bias. Stata Version 15.1 was used for data analysis.

Results: Thirty studies (24 cohort, 4 nested case-control and 2 case-control studies) were included covering 2,875,567 participants with the follow-up periods from 1 year to 18 years (Median=8.4 years). The pooled estimates of antidepressants use and new-onset T2DM were HR=1.24 (95% CI: 1.18, 1.31), RR=1.42 (95% CI: 0.99, 2.05) and OR=1.17 (95% CI: 1.03, 1.32), respectively. However, subgroup analyses showed that only tricyclic antidepressants (TCAs) use was positively associated with the new onset of T2DM in both cohort studies (combined RR=1.39, 95% CI: 1.17, 1.65) and case-control studies (combined OR=1.25, 95% CI: 1.05, 1.50). Moreover, the risk of T2DM was increased with the duration of antidepressants use in a linear trend (R= 88.51%, P = 0.009).

Limitations: Heterogeneity might impact the results and inference.

Conclusions: Antidepressants use might be a risk factor for the new onset of T2DM. Patients with long-term antidepressants use should be evaluated cautiously for T2DM risk. Routine T2DM screening is necessary in antidepressants users.