Comparing ischemic cardiovascular effectiveness and safety between individual SGLT-2 inhibitors and DPP-4 inhibitors in patients with type 2 diabetes: a nationwide population-based cohort study

Hayeon Kim; Jun-Ho Seo; Jin Hyun Nam; Yejee Lim; Kyung Hee Choi; Kyungim Kim

doi:10.3389/fphar.2024.1443175

Comparing ischemic cardiovascular effectiveness and safety between individual SGLT-2 inhibitors and DPP-4 inhibitors in patients with type 2 diabetes: a nationwide population-based cohort study

Front Pharmacol. 2024 Oct 30:15:1443175. doi: 10.3389/fphar.2024.1443175. eCollection 2024.

Authors

Hayeon Kim¹, Jun-Ho Seo², Jin Hyun Nam³, Yejee Lim⁴, Kyung Hee Choi⁵, Kyungim Kim^{1

6}

Affiliations

¹ College of Pharmacy, Korea University, Sejong, Republic of Korea.
² Department of Big Data Science, Korea University, Sejong, Republic of Korea.
³ Division of Big Data Science, Korea University, Sejong, Republic of Korea.
⁴ Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
⁵ College of Pharmacy, Gachon University, Incheon, Republic of Korea.
⁶ Institute of Pharmaceutical Science, Korea University, Sejong, Republic of Korea.

Abstract

Objectives: This study compared the ischemic cardiovascular events (iCVEs) effectiveness and safety of initiating empagliflozin or dapagliflozin with those of dipeptidyl peptidase-4 inhibitors (DPP-4is), as well as the comparative effects between empagliflozin and dapagliflozin.

Methods: Using data from the National Health Insurance Service in Korea, patients with type 2 diabetes mellitus (T2DM) who were newly prescribed empagliflozin, dapagliflozin, or DPP-4is from 2016 to 2019 and who did not have a recent CVE history were included. A Cox proportional hazards regression model was used to estimate the adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) for iCVEs and safety events.

Results: Empagliflozin and dapagliflozin significantly reduced the risks of ischemic stroke (aHR 0.568, 95% CI 0.408-0.791; aHR 0.612, 95% CI 0.476-0.786, respectively) and all-cause mortality (aHR 0.590, 95% CI 0.442-0.788; aHR 0.730, 95% CI 0.603-0.884, respectively) compared with DPP-4is. Initiating dapagliflozin or empagliflozin was associated with significantly lower incidence of severe hypoglycemia, bone fracture, urinary tract infection, and acute kidney injury than that of DPP-4is. No significant differences were observed between empagliflozin and dapagliflozin in iCVEs and most safety outcomes.

Conclusion: Empagliflozin and dapagliflozin showed significant preventive effects on ischemic stroke and all-cause mortality compared with DPP-4is in patients with T2DM, and their protective effects were similar. Both empagliflozin and dapagliflozin were not related to the harmful effects on most safety events. These results suggest that it may be beneficial to initiate empagliflozin or dapagliflozin for ischemic stroke prevention in patients with T2DM. However, further validation studies, such as randomized controlled trials, are needed to generalize these results.

Keywords: cardiovascular events; dapagliflozin; dipeptidyl-peptidase IV inhibitors; empagliflozin; retrospective study; sodium-glucose transporter 2 inhibitors.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (NRF-2020R1F1A1069257) and the Ministry of Education, Science and Technology (NRF-2019R1A6A1A03031807). The funders had no role in study design, data collection and analysis, interpretation of data, decision to publish, or preparation of the manuscript.