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Effects of ipragliflozin, a selective sodium–glucose co-transporter 2 inhibitor, on blood pressure in Japanese patients with type 2 diabetes mellitus: a pooled analysis of six randomized, placebo-controlled clinical trials

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Abstract

Our aim was to examine the effects of ipragliflozin, a selective sodium–glucose co-transporter 2 inhibitor, on blood pressure in Japanese patients with type 2 diabetes mellitus (T2DM). We conducted a pooled analysis of double-blind trials of Japanese T2DM patients, randomized to 50 mg ipragliflozin or placebo, with patient-level data for the change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) from baseline to end of treatment (12–24 weeks). Data from six trials were analyzed: ipragliflozin was administered as monotherapy in two; in combination with metformin, pioglitazone, or sulfonylurea in one each; and in combination with prior therapy in patients with renal impairment in one. Overall, 628 and 368 patients were treated with ipragliflozin and placebo, respectively. The placebo-adjusted mean changes (95 % confidence interval) in SBP and DBP (mmHg) were −2.8 (−4.4, −1.3, P < 0.001) and −1.6 (−2.7, −0.6, P < 0.002), respectively, in all patients. The reductions in SBP and DBP were significantly greater in patients with baseline SBP ≥140 mmHg [−5.5 (−9.1, −1.8) and −2.9 (−5.3, −0.5), respectively] than in patients with SBP <140 mmHg [−2.1 (−3.8, −0.4) and −1.3 (−2.5, −0.1), respectively]. The reductions in SBP and DBP were also significantly greater in the ipragliflozin group than in the placebo group in patients treated with [−2.8 (−5.1, −0.4) and −2.4 (−4.0, −0.8), respectively] or without [−3.0 (−5.0, −1.0) and −1.0 (−2.4, 0.4), respectively] concomitant antihypertensive therapy. In conclusion, this pooled analysis showed that ipragliflozin was associated with significant reductions in SBP and DBP compared with placebo.

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Acknowledgments

The authors wish to thank all of the investigators involved in each trial. This study was sponsored by Astellas Pharma Inc., Japan. Medical writing and editorial support was funded by Astellas and provided by Dr. Nicholas D. Smith (Edanz Group Ltd.) and Elsevier/ELMCOM™.

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Authors and Affiliations

  1. Kusatsu General Hospital, 1660 Yabase-cho, Kusatsu, Shiga, Japan

    Atsunori Kashiwagi

  2. Astellas Pharma Inc., Tokyo, Japan

    Satoshi Yoshida, Kosei Kawamuki, Ichiro Nakamura, Kenichi Kazuta, Eiji Ueyama, Hideyuki Takahashi & Noriko Akiyama

  3. Kotobuki Pharmaceutical Co., Ltd., Nagano, Japan

    Yoshinori Kondo

  4. Morinomiya University of Medical Sciences, Osaka, Japan

    Toshio Ogihara

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  1. Atsunori Kashiwagi
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Correspondence to Atsunori Kashiwagi.

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Conflict of interest

AK has acted as a consultant for Astellas Pharma Inc. and has received consulting fees/honoraria from Astellas Pharma Inc. TO has acted as a consultant for Kotobuki Pharmaceutical Co., Ltd., and has received consulting fees/honoraria from Kotobuki Pharmaceutical Co., Ltd. YK is an employee of Kotobuki Pharmaceutical Co., Ltd. The other authors are employees of Astellas Pharma Inc., Japan.

Human rights statement and informed consent

All included studies in this analysis were conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964 and later versions. Informed consent or a substitute for it was obtained from all patients for being included in the studies.

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Kashiwagi, A., Yoshida, S., Kawamuki, K. et al. Effects of ipragliflozin, a selective sodium–glucose co-transporter 2 inhibitor, on blood pressure in Japanese patients with type 2 diabetes mellitus: a pooled analysis of six randomized, placebo-controlled clinical trials. Diabetol Int 8, 76–86 (2017). https://doi.org/10.1007/s13340-016-0283-x

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