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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Clinical Diabetes
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1420485

Synergistically Improved Cardiovascular Outcomes in Type 2 Diabetes Mellitus Patients with Combined Treatment of SGLT-2 Inhibitors and Pioglitazone

Provisionally accepted
Yan-Rong Li Yan-Rong Li 1Chih-Ching Wang Chih-Ching Wang 1Chi-Hung Liu Chi-Hung Liu 1Chieh-Li Yen Chieh-Li Yen 1Victor Chien-Chia Wu Victor Chien-Chia Wu 1Evelyn Jou-Chen Huang Evelyn Jou-Chen Huang 2Ching Yu Lee Ching Yu Lee 2Ching-Chung Hsiao Ching-Chung Hsiao 3*
  • 1 Linkou Chang Gung Memorial Hospital, Linkou, Taiwan
  • 2 Taipei Medical University Hospital, Taipei, Taiwan
  • 3 New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan

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

    Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio.A total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs).Combined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54-0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49-1.07) compared with the reference group.In T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF.

    Keywords: type 2 diabetes mellitus, Sodium-Glucose Co-transporter-2 Inhibitors (SGLT2i), pioglitazone, cardiovascular outcomes, Heart Failure

    Received: 20 Apr 2024; Accepted: 12 Aug 2024.

    Copyright: © 2024 Li, Wang, Liu, Yen, Wu, Huang, Lee and Hsiao. 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: Ching-Chung Hsiao, New Taipei Municipal TuCheng Hospital, New Taipei City, 236, Taiwan

    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.