Comparative cardiovascular outcomes in type 2 diabetes patients taking dapagliflozin versus empagliflozin: a nationwide population-based cohort study

Abstract

Background Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. Methods Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. Results A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855–1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714–0.989) and cardiovascular death (HR 0.76, 95% CI 0.618–0.921), which were significantly lower in the dapagliflozin users. Conclusions This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus.

Efficacy of Sodium-Glucose Cotransporter 2 Inhibitors in Patients with Acute Coronary Syndrome

“…It should be noted that T2DM was the only cardiovascular risk factor in approximately 40% of participants. 42 In another pooled analysis, the effect of empagliflozin on cardiovascular mortality was reported to be more pronounced than that of dapagliflozin in patients with ASCVD. 7 Consequently, other possibilities, such as the cardiovascular status of patients and possible differences in baseline characteristics between the two subgroups, should be considered.…”

“…41 Clinical studies have shown that empagliflozin and dapagliflozin are inconsistent, especially in terms of cardiovascular death. 42 The inconsistency in cardiovascular death between empagliflozin and dapagliflozin may be due to the intrinsic pharmacological difference. Nevertheless, the SGLT2i subtype-specific difference has not yet been fully elucidated.…”

“…The different SGLT2i subtypes also differ in terms of efficacy and indication . Clinical studies have shown that empagliflozin and dapagliflozin are inconsistent, especially in terms of cardiovascular death . The inconsistency in cardiovascular death between empagliflozin and dapagliflozin may be due to the intrinsic pharmacological difference.…”

Cardiovascular outcomes between dapagliflozin versus empagliflozin in patients with diabetes mellitus

“…Additionally, another meta‐analysis study also indicated that empagliflozin was more beneficial in reducing mortality and cardiovascular events 22 . In contrast, some cohort studies showed no significant difference in overall MACE between the dapagliflozin and empagliflozin, but observed that dapagliflozin might be associated with lower risks hospitalization for heart failure 23,24 . The differences in outcomes across various studies might be attributed to differences in baseline comorbidities among the patients enrolled in these studies.…”

“…In a nationwide cohort study in Korea, it was shown that dapagliflozin might be more favorable in hospitalization for heart failure 23 . Although this study enrolled a large number of patients, the proportion of the study population with MI was 2.7%, and history of heart failure was 5.0%, which is lower compared to the landmark studies like EMPA‐REG OUTCOME trial and DAPA TIMI 58 trial 6,7,23 . Dapagliflozin group in DAPA TIMI 58 study showed that the rate of comorbidities of heart failure and coronary artery disease was 9.9% and 32.9%, respectively 6 .…”