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Comparison of the effects of linagliptin and voglibose on endothelial function in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, pilot study (EFFORT)

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Abstract

Endothelial dysfunction contributes to poor cardiovascular prognosis in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). The effect of dipeptidyl peptidase-4 inhibitors on endothelial function remains controversial. We sought to compare the effects of linagliptin and voglibose on endothelial function, as assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT). Sixteen patients with newly diagnosed T2DM and CAD were randomized 1:1 to linagliptin (5 mg, once-daily) or voglibose (0.9 mg, thrice-daily). The RH-PAT and laboratory parameters, including 75 g oral glucose tolerance test, were measured at baseline and 3 months. Linagliptin increased serum levels of active glucagon-like peptide-1 and high-molecular-weight adiponectin. Age-, sex-, and baseline-adjusted changes in logarithmic RH-PAT index (LnRHI) after 3 months were significant between groups (linagliptin, 0.135 ± 0.097; voglibose, − 0.124 ± 0.091; P = 0.047). In the linagliptin group, change in LnRHI was positively correlated with change in high-density lipoprotein cholesterol and negatively correlated with changes in both urine albumin-to-creatinine ratio and high-sensitivity C-reactive protein. Furthermore, linagliptin treatment for 3 months reduced serum levels of both glucose and insulin at 2 h, relative to voglibose, in the age-, sex-, and baseline-adjusted model. Linagliptin improved endothelial function relative to voglibose, accompanied by amelioration of glycemic, renal, and cardiometabolic parameters, in patients with newly diagnosed T2DM and CAD.

Trial registration Unique Trial Number, UMIN 000029169 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012442).

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Acknowledgements

Authors thank Mikiko Kagiyama, Sae Katafuchi, and Aya Yamada for their excellent secretarial assistance.

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Authors and Affiliations

  1. Department of Cardiology, Fukuoka Wajiro Hospital, Fukuoka, Japan

    Taku Koyama & Yoritaka Otsuka

  2. Department of Cardiovascular Medicine, Saga University, 5-5-1 Nabeshima, Saga, Japan

    Atsushi Tanaka, Jun-ichi Oyama & Koichi Node

  3. Clinical Research Center, Saga University, Saga, Japan

    Hisako Yoshida

  4. Department of Cardiovascular Medicine, Dokkyo Medical University, Mibu, Japan

    Shigeru Toyoda, Masashi Sakuma & Teruo Inoue

Authors
  1. Taku Koyama
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  2. Atsushi Tanaka
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  3. Hisako Yoshida
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  4. Jun-ichi Oyama
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  5. Shigeru Toyoda
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  6. Masashi Sakuma
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  7. Teruo Inoue
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  8. Yoritaka Otsuka
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  9. Koichi Node
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Corresponding authors

Correspondence to Atsushi Tanaka or Koichi Node.

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Conflict of interest

TK, AT, and HY have no financial interests to disclose related to this manuscript. JO has belonged to the research program faculty (chair course) sponsored by Fukuda Denshi. ST and MS have no financial interests to disclose related to this manuscript. 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. YO has no financial interests to disclose related to this manuscript. KN 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.

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Koyama, T., Tanaka, A., Yoshida, H. et al. Comparison of the effects of linagliptin and voglibose on endothelial function in patients with type 2 diabetes and coronary artery disease: a prospective, randomized, pilot study (EFFORT). Heart Vessels 33, 958–964 (2018). https://doi.org/10.1007/s00380-018-1136-2

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