Efficacy and safety of selective serotonin reuptake inhibitors for diabetes mellitus with depression: a systematic review and meta-analysis.
To evaluate the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) in patients with diabetes mellitus and comorbid depression.
This study was registered in PROSPERO (CRD420261305439). Eight electronic databases were searched up to February 11, 2026 for randomized controlled trials comparing SSRIs plus usual care versus control. Outcomes included depressive symptoms (HDRS, BDI), anxiety (HARS), glycaemic control (HbA1c, FPG, PPG), and BMI. Meta-analyses were performed using random-effects models; subgroup analysis by follow-up duration and sensitivity analysis were conducted.
Nine RCTs (770 participants) were included. Overall, SSRIs did not significantly improve HDRS (MD = 0.16, 95% CI -0.69 to 1.01, P = 0.72) or BDI scores. However, subgroup analysis showed significant HDRS reduction when follow-up was ≥ 6 months (MD = -0.96, 95% CI -1.86 to -0.05, P = 0.04). SSRIs were associated with increased HARS scores (MD = 2.37, 95% CI 0.73 to 4.02, P = 0.005). No significant effects were observed for HbA1c, FPG, PPG, or BMI.
Preliminary evidence suggests that SSRIs may offer modest antidepressant benefits when used for ≥ 6 months in diabetic patients with depression, but they may be associated with a small increase in anxiety scores and do not appear to improve glycaemic control or BMI. However, the overall certainty of evidence is low to moderate. Monitoring of early anxiety symptoms is recommended, and further high-quality RCTs are needed.
https://www.crd.york.ac.uk/prospero/, identifier CRD420261305439.
This study was registered in PROSPERO (CRD420261305439). Eight electronic databases were searched up to February 11, 2026 for randomized controlled trials comparing SSRIs plus usual care versus control. Outcomes included depressive symptoms (HDRS, BDI), anxiety (HARS), glycaemic control (HbA1c, FPG, PPG), and BMI. Meta-analyses were performed using random-effects models; subgroup analysis by follow-up duration and sensitivity analysis were conducted.
Nine RCTs (770 participants) were included. Overall, SSRIs did not significantly improve HDRS (MD = 0.16, 95% CI -0.69 to 1.01, P = 0.72) or BDI scores. However, subgroup analysis showed significant HDRS reduction when follow-up was ≥ 6 months (MD = -0.96, 95% CI -1.86 to -0.05, P = 0.04). SSRIs were associated with increased HARS scores (MD = 2.37, 95% CI 0.73 to 4.02, P = 0.005). No significant effects were observed for HbA1c, FPG, PPG, or BMI.
Preliminary evidence suggests that SSRIs may offer modest antidepressant benefits when used for ≥ 6 months in diabetic patients with depression, but they may be associated with a small increase in anxiety scores and do not appear to improve glycaemic control or BMI. However, the overall certainty of evidence is low to moderate. Monitoring of early anxiety symptoms is recommended, and further high-quality RCTs are needed.
https://www.crd.york.ac.uk/prospero/, identifier CRD420261305439.