Heart and Vessels

, Volume 33, Issue 9, pp 965–977 | Cite as

Effect of pioglitazone on cardiometabolic profiles and safety in patients with type 2 diabetes undergoing percutaneous coronary artery intervention: a prospective, multicenter, randomized trial

  • Atsushi TanakaEmail author
  • Sho Komukai
  • Yoshisato Shibata
  • Hiroyoshi Yokoi
  • Yoshihiro Iwasaki
  • Tomohiro Kawasaki
  • Kenji Horiuchi
  • Koichi Nakao
  • Takafumi Ueno
  • Hitoshi Nakashima
  • Masahiro Tamashiro
  • Yutaka Hikichi
  • Mitsuhiro Shimomura
  • Motoko Tago
  • Shigeru Toyoda
  • Teruo Inoue
  • Atsushi Kawaguchi
  • Koichi NodeEmail author
  • On behalf of the Pioglitazone Reduce Inflammation and Restenosis with and without Drug Eluting Stent (PRIDE) Study Investigators
Original Article


Pioglitazone has superior antiatherosclerotic effects compared with other classes of antidiabetic agents, and there is substantial evidence that pioglitazone improves cardiovascular (CV) outcomes. However, there is also a potential risk of worsening heart failure (HF). Therefore, it is clinically important to determine whether pioglitazone is safe in patients with type 2 diabetes mellitus (T2DM) who require treatment for secondary prevention of CV disease, since they have an intrinsically higher risk of HF. This prospective, multicenter, open-label, randomized study investigated the effects of pioglitazone on cardiometabolic profiles and CV safety in T2DM patients undergoing elective percutaneous coronary intervention (PCI) using bare-metal stents or first-generation drug-eluting stents. A total of 94 eligible patients were randomly assigned to either a pioglitazone or conventional (control) group, and pioglitazone was started the day before PCI. Cardiometabolic profiles were evaluated before PCI and at primary follow-up coronary angiography (5–8 months). Pioglitazone treatment reduced HbA1c levels to a similar degree as conventional treatment (pioglitazone group 6.5 to 6.0%, P < 0.01; control group 6.5 to 5.9%, P < 0.001), without body weight gain. Levels of high-molecular weight adiponectin increased more in the pioglitazone group than the control group (P < 0.001), and the changes were irrespective of baseline glycemic control. Furthermore, pioglitazone significantly reduced plasma levels of natriuretic peptides and preserved cardiac systolic and diastolic function (assessed by echocardiography) without incident hospitalization for worsening HF. The incidence of clinical adverse events was also comparable between the groups. These results indicate that pioglitazone treatment before and after elective PCI may be tolerable and clinically safe and may improve cardiometabolic profiles in T2DM patients.


Pioglitazone Type 2 diabetes mellitus Adiponectin Cardiac function Percutaneous coronary intervention 



This study was partly supported by JSPS KAKENHI Grant Number 17K09510. The authors thank Sae Katafuchi and Aya Yamada for their excellent secretarial assistance.

Compliance with ethical standards

Conflict of interest

HY has received honoraria from Takeda. TU has received honoraria from Daiichi Sankyo, Bayer, Mochida, Boehringer Ingelheim; research funding from Daiichi Sankyo. TI has received honoraria from Mochida and Bayer; and scholarships from Abbott, KAATHU JAPAN, GOODMAN, CLINICO, Shionogi, St. Jude Medical, Daiichi Sankyo, Takeda, Mitsubishi Tanabe, Teijin, Boehringer Ingelheim, Boston Scientific Japan, and UNION TOOL. KNo has received honoraria from Daiichi Sankyo, Merck, Pfizer, Eli Lilly, Amgen, Boehringer Ingelheim, Mitsubishi Tanabe, and Astellas; research funding from Bayer, Teijin, Mitsubishi Tanabe, Astellas, Boehringer Ingelheim, and Asahi Kasei; and scholarships from Astellas, Daiichi Sankyo, Sumitomo Dainippon, Takeda, Mitsubishi Tanabe, and Boehringer Ingelheim. The remaining authors have no financial interests to disclose related to this manuscript.


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Copyright information

© Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  • Atsushi Tanaka
    • 1
    Email author
  • Sho Komukai
    • 2
  • Yoshisato Shibata
    • 3
  • Hiroyoshi Yokoi
    • 4
  • Yoshihiro Iwasaki
    • 5
  • Tomohiro Kawasaki
    • 6
  • Kenji Horiuchi
    • 7
  • Koichi Nakao
    • 7
  • Takafumi Ueno
    • 8
  • Hitoshi Nakashima
    • 9
  • Masahiro Tamashiro
    • 10
  • Yutaka Hikichi
    • 1
  • Mitsuhiro Shimomura
    • 1
  • Motoko Tago
    • 1
  • Shigeru Toyoda
    • 11
  • Teruo Inoue
    • 11
  • Atsushi Kawaguchi
    • 2
  • Koichi Node
    • 1
    Email author
  • On behalf of the Pioglitazone Reduce Inflammation and Restenosis with and without Drug Eluting Stent (PRIDE) Study Investigators
  1. 1.Department of Cardiovascular MedicineSaga UniversitySagaJapan
  2. 2.Clinical Research CenterSaga University HospitalSagaJapan
  3. 3.Miyazaki Medical Association Hospital, Cardiovascular CenterMiyazakiJapan
  4. 4.Department of CardiologyKokura Memorial HospitalKitakyushuJapan
  5. 5.Department of CardiologyNagasaki Kouseikai HospitalNagasakiJapan
  6. 6.Department of Cardiology, Cardiovascular CenterShin-Koga HospitalKurumeJapan
  7. 7.Division of CardiologySaiseikai Kumamoto Hospital Cardiovascular CenterKumamotoJapan
  8. 8.Division of Cardiovascular Medicine, Department of Internal MedicineKurume University School of MedicineKurumeJapan
  9. 9.Department of CardiologyNational Hospital Organization Kagoshima Medical CenterKagoshimaJapan
  10. 10.Department of CardiologyTomishiro Central HospitalOkinawaJapan
  11. 11.Department of Cardiovascular MedicineDokkyo Medical UniversityMibuJapan

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