Association between sodium glucose co-transporter 2 inhibitors and a reduced risk of heart failure in patients with type 2 diabetes mellitus: a real-world nationwide population-based cohort study

Cardiovasc Diabetol. 2018 Jun 23;17(1):91. doi: 10.1186/s12933-018-0737-5.


Background: Recently, two large randomized controlled trials which only included patients with underlying cardiovascular disease (CVD) or patients at high risk for CVD showed that two sodium glucose co-transporter 2 inhibitors (SGLT-2is) significantly reduced hospitalization for heart failure (hHF), with an early separation in the survival curves for hHF. There were concerns whether SGLT-2i use could protect hHF in patients without CVD and how soon SGLT-2i-treated patients show a lower risk of hHF. Thus, we aimed to evaluate whether the heart failure protective effect of SGLT-2i differs depending on the underlying CVD and the prescription period compared with dipeptidyl peptidase-4 inhibitors (DPP-4i).

Methods: We performed a nationwide retrospective observational study to estimate the effect of SGLT-2i on HF. The 59,479 SGLT-2i new-users were matched with same number of DPP-4i new-users through propensity score matching using 53 confounding variables. Kaplan-Meier (K-M) curves and Cox proportional hazards regression analyses were used to estimate the risk of hospitalization for hHF.

Results: The incidence rates of hHF were 0.83 and 1.13 per 100 person-years in SGLT-2i-treated patients and DPP-4i-treated patients, respectively. The hazard ratios of hHF were 0.66 (95% confidence interval 0.58-0.75) in SGLT-2i-treated patients compared with the DPP-4i-treated patients. Among the patients with underlying CVD, SGLT-2i-treated patients were associated with a lower risk of hHF from 30 days to 3 years after initiating drugs compared with DPP-4i. However, SGLT-2i use only showed a lower risk of hHF with a significant difference 3 years after drug initiation among patients without underlying CVD.

Conclusions: Our findings suggest that SGLT-2i reduced hHF compared with DPP-4i. A heart failure protective effect of SGLT-2i use vs. DPP-4i use was shown 30 days after initiating the SGLT-2i among patients with established CVD, but this effect appeared later in patients without established CVD.

Keywords: Heart failure; Sodium glucose co-transporter 2 inhibitors dipeptidyl peptidase-4 inhibitor; Type 2 diabetes mellitus.

Publication types

  • Comparative Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Female
  • Heart Failure / diagnosis
  • Heart Failure / epidemiology
  • Heart Failure / prevention & control*
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Protective Factors
  • Republic of Korea
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Time Factors
  • Treatment Outcome


  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors