Incident heart failure and myocardial infarction in sodium-glucose cotransporter-2 vs. dipeptidyl peptidase-4 inhibitor users

Abstract

Aims: This study aimed to compare the rates of major cardiovascular adverse events in sodium-glucose cotransporter-2 inhibitors (SGLT2I) and dipeptidyl peptidase-4 inhibitors (DPP4I) users in a Chinese population. SGLT2I and DPP4I are increasingly prescribed for type 2 diabetes mellitus patients. However, few population-based studies are comparing their effects on incident heart failure or myocardial infarction.

Methods and results: This was a population-based retrospective cohort study using the electronic health record database in Hong Kong, including type 2 diabetes mellitus patients receiving either SGLT2I or DPP4I from 1 January 2015 to 31 December 2020. Propensity score matching was performed in a 1:1 ratio based on demographics, past comorbidities, and non-SGLT2I/DPP4I medications with nearest neighbour matching (caliper = 0.1). Univariable and multivariable Cox models were used to identify significant predictors for new-onset heart failure, new-onset myocardial infarction, cardiovascular mortality, and all-cause mortality. Sensitivity analyses with competing risk models and multiple propensity score matching approaches were conducted. A total of 41 994 patients (58.89% males, median admission age at 58 years old, interquartile range [IQR]: 51.2-65.3) were included with a median follow-up of 5.6 years (IQR: 5.32-5.82). In the matched cohort, SGLT2I use was significantly associated with lower risks of new-onset heart failure (hazard ratio [HR]: 0.73, 95% confidence interval [CI]: [0.66, 0.81], P < 0.0001), myocardial infarction (HR: 0.81, 95% CI: [0.73, 0.90], P < 0.0001), cardiovascular mortality (HR: 0.67, 95% CI: [0.53, 0.84], P < 0.001), and all-cause mortality (HR: 0.26, 95% CI: [0.24, 0.29], P < 0.0001) after adjusting for significant demographics, past comorbidities, and non-SGLT2I/DPP4I medications.

Conclusions: SGLT2 inhibitors are protective against adverse cardiovascular events including new-onset heart failure, myocardial infarction, cardiovascular mortality, and all-cause mortality. The prescription of SGLT2I is preferred when taken into consideration individual cardiovascular and metabolic risk profiles in addition to drug-drug interactions.

Keywords: Diabetes mellitus; Heart failure; Myocardial infarction; Sodium-glucose co-transporter.

Figure 1

Flowchart of data processing. DPP4I, dipeptidyl peptidase‐4 inhibitors; IR, incidence rate; SGLT2I, sodium‐glucose cotransporter‐2 inhibitors.

Figure 2

Cumulative incidence curves for heart failure, myocardial infarction, cardiovascular mortality, and all‐cause mortality stratified by SGLT2I or DPP4I use in the matched cohort. DPP4I, dipeptidyl peptidase‐4 inhibitors; SGLT2I, sodium‐glucose cotransporter‐2 inhibitors.