Comparing sodium-glucose cotransporter 2 inhibitors and dipeptidyl peptidase-4 inhibitors on new-onset depression: a propensity score-matched study in Hong Kong

Acta Diabetol. 2023 Jul;60(7):917-927. doi: 10.1007/s00592-023-02063-6. Epub 2023 Mar 31.

Abstract

Introduction: The risk of new onset depression associated with sodium-glucose co-transporter 2 inhibitor (SGLT2I) use in patients with type 2 diabetes mellitus (T2DM) remains unclear. This study investigated the risk of new onset depression between SGLT2I and dipeptidyl peptidase 4 inhibitor (DPP4I) users.

Methods: This was a population-based cohort study of T2DM patients in Hong Kong between January 1st, 2015, and December 31st, 2019. T2DM patients over 18 with either SGLT2I or DPP4I use were included. 1:1 propensity-score matching using the nearest-neighbour method was conducted based on demographics, past comorbidities and non-DPP4I/SGLT2I medication use. Cox regression analysis models were used to identify significant predictors for new onset depression.

Results: The study cohort included a total of 18,309 SGLT2I users and 37,269 DPP4I users (55.57% male, mean age: 63.5 ± 12.9 years) with a median follow-up duration of 5.56 (IQR: 5.23-5.8) years. After propensity score matching, SGLT2I use was associated with a lower risk of new onset depression compared to DPP4I use (HR: 0.52, 95% CI: [0.35, 0.77], P = 0.0011). These findings were confirmed by Cox multivariable analysis and sensitive analyses.

Conclusion: SGLT2I use is associated with significantly lower risk of depression compared to DPP4 use in T2DM patients using propensity score matching and Cox regression analyses.

Keywords: Anti-diabetic medication; DPP4 inhibitor; Depression; SGLT2 inhibitor; Type 2 diabetes.

MeSH terms

  • Aged
  • Cohort Studies
  • Depression / drug therapy
  • Depression / epidemiology
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors* / adverse effects
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / therapeutic use
  • Female
  • Glucose
  • Hong Kong / epidemiology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Middle Aged
  • Propensity Score
  • Retrospective Studies
  • Sodium / therapeutic use
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Sodium-Glucose Transporter 2 Inhibitors
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • Glucose
  • Sodium