Clinical epidemiology · 2025
Sodium-Glucose Cotransporter 2 Inhibitors and Lower Risk of Depression in Population with Type 2 Diabetes Mellitus: A Population-Based Active Comparator, New-User Design.
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Kao Ming-Jyun, Huang Ying-Chih, Huang Yu-Chieh, Yang Hui-Wen, To Sheng-Yin, Liao Chun-Cheng, Wen Yuan-Liang, Kao Li-Ting
Аннотация
PURPOSE: This study aimed to investigate the association between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) and the risk of developing depression in patients with type 2 diabetes mellitus.
PATIENTS AND METHODS: This study used Taiwan's National Health Insurance Database and an active comparator new-user design to evaluate depression risk among 551,917 patients initiating SGLT2i or DPP4i between 2016 and 2018. The primary outcome was depression incidence, assessed over a three-year follow-up. Stratified Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) between groups.
RESULTS: Among new SGLT2i users, 3255 cases of depression occurred (7.18 per 1000 person-years) versus 7190 cases among DPP4i users (10.12 per 1000 person-years). After adjustment for demographic and clinical covariates, SGLT2i use was consistently associated with a lower risk of depression in both the full cohort (adjusted HR = 0.77; 95% CI: 0.73-0.80) and the propensity score-matched cohort (adjusted HR = 0.77; 95% CI: 0.74-0.81). The association remained robust in multiple sensitivity analyses and across clinical subgroups.
CONCLUSION: SGLT2i use was associated with a reduced risk of depression among individuals with type 2 diabetes mellitus. These findings suggest potential neuropsychiatric benefits of SGLT2i and support further investigation into their broader therapeutic implications.
PATIENTS AND METHODS: This study used Taiwan's National Health Insurance Database and an active comparator new-user design to evaluate depression risk among 551,917 patients initiating SGLT2i or DPP4i between 2016 and 2018. The primary outcome was depression incidence, assessed over a three-year follow-up. Stratified Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) between groups.
RESULTS: Among new SGLT2i users, 3255 cases of depression occurred (7.18 per 1000 person-years) versus 7190 cases among DPP4i users (10.12 per 1000 person-years). After adjustment for demographic and clinical covariates, SGLT2i use was consistently associated with a lower risk of depression in both the full cohort (adjusted HR = 0.77; 95% CI: 0.73-0.80) and the propensity score-matched cohort (adjusted HR = 0.77; 95% CI: 0.74-0.81). The association remained robust in multiple sensitivity analyses and across clinical subgroups.
CONCLUSION: SGLT2i use was associated with a reduced risk of depression among individuals with type 2 diabetes mellitus. These findings suggest potential neuropsychiatric benefits of SGLT2i and support further investigation into their broader therapeutic implications.