The Association Between Selective Serotonin Reuptake Inhibitors and Glycemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objective Individual studies have reported conflicting effects of selective serotonin reuptake inhibitors (SSRIs) on glycemia. We systematically reviewed the effects of SSRIs on glycemia and whether metabolic and psychological factors moderated these effects. Methods We systematically searched for placebo-controlled randomized controlled trials investigating the effect of SSRIs on glycemia (fasting blood glucose or HbA1c) as a primary or secondary outcome. Random effects meta-analysis was conducted to compute an overall treatment effect. Meta-regression tested whether depression, type 2 diabetes, insulin resistance, treatment duration, and weight loss moderated treatment effects. Results Sixteen randomized controlled trials (n = 835) were included and glycemia was usually a secondary outcome. Overall, SSRIs improved glycemia versus placebo (pooled effect size (ES) = -0.34, 95% confidence interval (CI) = -0.48 to -0.21; p < .001, I-2 = 0%). Individually, fluoxetine (ES = -0.29, 95% CI = -0.54 to -0.05; p = .018) and escitalopram/citalopram (ES = -0.33, 95% CI = -0.59 to -0.07; p = .012) outperformed placebo, but paroxetine (ES = -0.19, 95% CI = -0.58 to 0.19; p = .33) did not. Results were similar in populations selected for depression as those not. Across studies, baseline insulin resistance (p = .46), treatment duration (p = .47), diabetes status (p = .41), and weight loss (p = .93) did not moderate changes. Heterogeneity for all analyses was nonsignificant. Conclusions SSRIs seem to have an association with improvement in glycemia, which is not moderated by depression status, diabetes status, or change in weight across studies. Future powered trials with longer treatment duration are needed to confirm these findings. Registration PROSPERO ID: CRD4201809239.