Comparison of cardiovascular outcomes between SGLT2 inhibitors in diabetes mellitus

Abstract

Background: There have been scarce data comparing cardiovascular outcomes between individual sodium-glucose cotransporter-2 (SGLT2) inhibitors. We aimed to compare the subsequent cardiovascular risk between individual SGLT2 inhibitors.

Methods: We analyzed 25,315 patients with diabetes mellitus (DM) newly taking SGLT2 inhibitors (empagliflozin: 5302, dapagliflozin: 4681, canagliflozin: 4411, other SGLT2 inhibitors: 10,921). We compared the risks of developing heart failure (HF), myocardial infarction (MI), angina pectoris (AP), stroke, and atrial fibrillation (AF) between individual SGLT2 inhibitors.

Results: Median age was 52 years, and 82.5% were men. The median fasting plasma glucose and HbA1c levels were 149 (Q1-Q3:127-182) mg/dL and 7.5 (Q1-Q3:6.9-8.6) %. During a mean follow-up of 814 ± 591 days, 855 HF, 143 MI, 815 AP, 340 stroke, and 139 AF events were recorded. Compared with empagliflozin, the risk of developing HF, MI, AP, stroke, and AF was not significantly different in dapagliflozin, canagliflozin, and other SGLT inhibitors. For developing HF, compared with empagliflozin, hazard ratios of dapagliflozin, canagliflozin, and other SGLT2 inhibitors were 1.02 (95% confidence interval [CI] 0.81-1.27), 1.08 (95% CI 0.87-1.35), and 0.88 (95% CI 0.73-1.07), respectively. Wald tests showed that there was no significant difference in the risk of developing HF, MI, AP, stroke, and AF among individual SGLT2 inhibitors. We confirmed the robustness of these results through a multitude of sensitivity analyses.

Conclusion: The risks for subsequent development of HF, MI, AP, stroke, and AF were comparable between individual SGLT2 inhibitors. This is the first study comparing the wide-range cardiovascular outcomes of patients with DM treated with individual SGLT2 inhibitors using large-scale real-world data.

Keywords: Cardiovascular disease; Diabetes mellitus; SGLT2 inhibitor.

Fig. 1

Flowchart. We extracted data on 37,283 individuals with diabetes mellitus (ICD-10 codes: E10−E14) who had started taking sodium-glucose cotransporter-2 inhibitors at least 4 months after enrollment (insurance coverage). Among them, we excluded individuals aged < 20 years (n = 4), those with a prior history of cardiovascular disease or renal failure (n = 7594), those who recorded any cardiovascular disease events or were censored within an induction period (1 month) (n = 1229), those with missing data on cigarette smoking (n = 752), and those with missing data on alcohol consumption (n = 2389). Finally, we analyzed 25,315 individuals in this study

Fig. 2

Risk of Cardiovascular Event among SGLT2 Inhibitors. We compared the risks of HF, MI, AP, stroke, and AF between individual SGLT2 inhibitors. Incidence rates were presented as per 10,000 person-years

Fig. 3

Risk of Heart Failure among SGLT2 Inhibitors (Subgroup analysis). We compared the risk of HF between individual SGLT2 inhibitors stratified by sex, age, and baseline HbA1c level. Sex was excluded from the adjusted variables in the subgroup analysis stratified by sex. We excluded 1772 individuals with missing HbA1c data from the subgroup analysis stratified by HbA1c level. Incidence rates were presented as per 10,000 person-years