Contemporary use of SGLT2 inhibitors in heart failure patients with diabetes mellitus: a comparison of DPP4 inhibitors in a nationwide electric health database of the superaged society

Abstract

Background: There is a lack of recent data reflecting the actual use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for heart failure (HF) and type 2 diabetes (DM) in the superaged society. The present study investigated the association between the use of SGLT2 inhibitors and one-year prognosis in patients hospitalized across a broad spectrum of HF patients with DM in the superaged society using the Nationwide Electric Health Database in Japan.

Methods: The patients hospitalized with the first episode of acute HF were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan between April 2014 and March 2019. A cohort of 2,277 users of SGLT2 inhibitors and 41,410 users of the active comparator, dipeptidyl peptidase-4 (DPP4) inhibitors were compared. A propensity score-matched cohort study of 2,101 users of each inhibitor was also conducted. A multivariable multilevel mixed-effects survival model was conducted with adjustments, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Results: Among 300,398 patients discharged with HF in 4,176 hospitals, 216,016 (71.9%) were 75 years or older, and 60,999 (20.3%) took antidiabetic medications. Among them, the patients treated with SGLT2 inhibitors were younger and had a more severe status than those treated with DPP4 inhibitors. Kaplan-Meier analysis showed that patients treated with SGLT2 inhibitors had a lower mortality risk and HF readmission. In propensity-matched cohorts, SGLT2 inhibitor use was associated with a lower risk of mortality and HF readmission than DPP-4 inhibitor use (HR [95% CI]; 0.70 [0.56, 0.89] and 0.52 [0.45, 0.61], respectively). Very elderly (≥ 75 years) patients showed similar results. Favorable effects were also observed across all age groups, including ≥ 75 years, in patients with coronary artery disease or atrial fibrillation and with concomitant β-blocker, diuretics, or insulin.

Conclusion: The use of SGLT2 inhibitors at discharge was associated with a lower risk of one-year mortality and HF readmission in patients across a broad spectrum of HF with DM in the superaged society. The findings further support the benefits of using SGLT2 inhibitors in very elderly HF care and complement the current evidence.

Keywords: An SGLT2 inhibitor; Diabetes mellitus; Nationwide Electric Health Database; One-year prognosis; Superaged society.

Fig. 1

Study flow chart. DM, diabetes mellitus; DPP4, dipeptidyl peptidase-4; HF, heart failure: SGLT2, sodium-glucose cotransporter-2

Fig. 2

Kaplan–Meier analysis of all-cause mortality (a) and HF readmission (b) for SGLT2 and DPP4 inhibitor use at discharge in overall patients and in patients aged ≥ 75 years. DPP4-I, dipeptidyl peptidase-4 inhibitor; HF, heart failure: SGLT2-I, sodium-glucose cotransporter-2 inhibitor

Fig. 3

Stratified analysis for all-cause mortality (a) and HF readmission (b) in the propensity-matched cohort. AF, atrial fibrillation or atrial flutter; CAD, coronary artery disease; CI, confidence interval; DPP4, dipeptidyl peptidase-4; HF, heart failure; SGLT2, sodium-glucose cotransporter-2