The association between selective serotonin reuptake inhibitors and glycemia: a systematic review and meta-analysis of randomized controlled trials

TY - JOUR

T1 - The association between selective serotonin reuptake inhibitors and glycemia

T2 - a systematic review and meta-analysis of randomized controlled trials

AU - Tharmaraja, Thahesh

AU - Stahl, Daniel

AU - Hopkins, Christopher

AU - Persaud, Shanta Jean

AU - Jones, Peter M.

AU - Ismail, Khalida

AU - Moulton, Calum

PY - 2019/9/1

Y1 - 2019/9/1

N2 - Objective:Individual studies have reported conflicting effects of selective serotonin reuptake inhibitors (SSRIs) on glycaemia. 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 randomised controlled trials (RCTs) investigating the effect of SSRIs on glycaemia (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 RCTs (n=835) were included and glycaemia was usually a secondary outcome. Overall, SSRIs improved glycaemia versus placebo (pooled effect size (ES)=-0.34, 95% confidence interval (CI) -0.48 to -0.21; p < 0.001, I^2 =0%). Individually, fluoxetine (ES=-0.29, 95% CI -0.54 to -0.05; p=0.018) and escitalopram/citalopram (ES=-0.33, 95% CI -0.59 to -0.07; p=0.012) outperformed placebo, but paroxetine (ES=-0.19, 95% CI -0.58 to 0.19; p=0.33) did not. Results were similar in populations selected for depression as those not. Across studies, baseline insulin resistance (p=0.46), treatment duration (p=0.47), diabetes status (p=0.41) and weight loss (p=0.93) did not moderate changes. Heterogeneity for all analyses was non-significant. Conclusions: SSRIs appear to have an association with improvement in glycaemia, 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

AB - Objective:Individual studies have reported conflicting effects of selective serotonin reuptake inhibitors (SSRIs) on glycaemia. 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 randomised controlled trials (RCTs) investigating the effect of SSRIs on glycaemia (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 RCTs (n=835) were included and glycaemia was usually a secondary outcome. Overall, SSRIs improved glycaemia versus placebo (pooled effect size (ES)=-0.34, 95% confidence interval (CI) -0.48 to -0.21; p < 0.001, I^2 =0%). Individually, fluoxetine (ES=-0.29, 95% CI -0.54 to -0.05; p=0.018) and escitalopram/citalopram (ES=-0.33, 95% CI -0.59 to -0.07; p=0.012) outperformed placebo, but paroxetine (ES=-0.19, 95% CI -0.58 to 0.19; p=0.33) did not. Results were similar in populations selected for depression as those not. Across studies, baseline insulin resistance (p=0.46), treatment duration (p=0.47), diabetes status (p=0.41) and weight loss (p=0.93) did not moderate changes. Heterogeneity for all analyses was non-significant. Conclusions: SSRIs appear to have an association with improvement in glycaemia, 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

KW - Abbreviations

KW - CI = confidence interval

KW - ES = effect size

KW - HOMA = Homeostatic Model Assessment

KW - RCT = randomized controlled trial

KW - SMD = standardized mean difference

KW - SSRI = selective serotonin reuptake inhibitors

KW - depression

KW - diabetes

KW - insulin resistance

KW - meta-Analysis

KW - meta-regression

KW - systematic review

UR - http://www.scopus.com/inward/record.url?scp=85071714464&partnerID=8YFLogxK

U2 - 10.1097/PSY.0000000000000707

DO - 10.1097/PSY.0000000000000707

M3 - Review article

SN - 0033-3174

VL - 81

SP - 570

EP - 583

JO - Psychosomatic Medicine

JF - Psychosomatic Medicine

IS - 7

ER -