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

Abstract

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.

Fig. 1

Flow chart of the sample selection, stratified by underlying cardiovascular disease. CVD cardiovascular disease, DM diabetes mellitus, DPP-4i dipeptidyl-peptidase IV inhibitor, N number, SGLT-2i sodium-glucose co-transporter 2 inhibitor

Fig. 2

Kaplan–Meier plots of hospitalization for heart failure in all patients (a) and baseline cardiovascular stratifications (b with baseline cardiovascular disease, c without baseline cardiovascular disease). DPP-4i dipeptidyl-peptidase IV inhibitor, N number, SGLT-2i sodium-glucose co-transporter 2 inhibitor, y year(s)