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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Pharmacoepidemiology
Volume 15 - 2024 | 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

Provisionally accepted
Hayeon Kim Hayeon Kim 1Junho Seo Junho Seo 2Jin Hyun Nam Jin Hyun Nam 2Yejee Lim Yejee Lim 3Kyung Hee Choi Kyung Hee Choi 4Kyungim Kim Kyungim Kim 1,5*
  • 1 College of Pharmacy, Korea University, Sejong, Republic of Korea
  • 2 Division of Big Data Science, Korea University, Sejong, Republic of Korea
  • 3 Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea
  • 4 College of Pharmacy, Gachon University, Incheon, Republic of Korea
  • 5 Institute of Pharmaceutical Science, Korea University, Sejong, Republic of Korea

The final, formatted version of the article will be published soon.

    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: sodium-glucose transporter 2 inhibitors, empagliflozin, dapagliflozin, Dipeptidylpeptidase IV inhibitors, cardiovascular events, Retrospective study

    Received: 03 Jun 2024; Accepted: 15 Oct 2024.

    Copyright: © 2024 Kim, Seo, Nam, Lim, Choi and Kim. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Kyungim Kim, College of Pharmacy, Korea University, Sejong, Republic of Korea

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.