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Efficacy and safety of ipragliflozin as an add-on to pioglitazone in Japanese patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study (the SPOTLIGHT study)

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Abstract

Ipragliflozin is a novel oral sodium–glucose cotransporter 2 (SGLT2) inhibitor under development for the treatment of type 2 diabetes. We examined its efficacy and safety as an add-on to pioglitazone in Japanese patients with inadequately controlled diabetes. Japanese type 2 diabetes patients were randomized to 24 weeks of treatment with 50 mg ipragliflozin or placebo in a double-blind manner. At week 24, patients with hemoglobin (Hb)A1c <8.4 % were permitted to continue open-label ipragliflozin in a 28-week extension period. The primary endpoint was the change in HbA1c from baseline to week 24 (with last observation carried forward). Ninety-eight and 54 patients were randomized to ipragliflozin or placebo, respectively, and were prescribed the study drug. The mean HbA1c change from baseline to week 24 was −0.64 % and 0.22 % in the ipragliflozin and placebo groups, respectively, and the adjusted mean difference between the two groups was −0.88 % (P < 0.001). Changes in fasting plasma glucose (FPG) and body weight were significantly greater in the ipragliflozin group (both P < 0.001). Among patients who continued ipragliflozin in the extension period, reductions in HbA1c, FPG, and body weight were maintained until week 52. The incidence of treatment-emergent adverse events was not significantly different between the two groups. The most common event with a higher incidence in the ipragliflozin group than in the placebo group was pollakiuria (12/97 vs. 0/54 patients). Ipragliflozin improved glycemic control, promoted weight reduction, and had a good safety profile as an add-on to pioglitazone in Japanese type 2 diabetes patients.

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Acknowledgments

Ipragliflozin is under development by Astellas Pharma Inc. and Kotobuki Pharmaceutical Co., Ltd. This study was sponsored by Astellas Pharma Inc. Medical writing and editorial support was funded by Astellas Pharma Inc., and was provided by Dr. Nicholas D. Smith and ELMCOM™.

Conflict of interest

TS, NA, KK, AU, SY, and EU are employees of Astellas Pharma Inc. AK has acted as a consultant for Astellas Pharma Inc. and has received consulting fees/honoraria from Astellas Pharma Inc.

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Authors and Affiliations

  1. Shiga University of Medical Science, Shiga, Japan

    Atsunori Kashiwagi

  2. Astellas Pharma Inc, 2-5-1, Nihonbashi-Honcho, Chuo-ku, Tokyo, 103-8411, Japan

    Takanori Shiga, Noriko Akiyama, Kenichi Kazuta, Atsushi Utsuno, Satoshi Yoshida & Eiji Ueyama

Authors
  1. Atsunori Kashiwagi
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  2. Takanori Shiga
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  3. Noriko Akiyama
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  4. Kenichi Kazuta
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  5. Atsushi Utsuno
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  6. Satoshi Yoshida
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  7. Eiji Ueyama
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Corresponding author

Correspondence to Noriko Akiyama.

Appendix

Appendix

Primary investigators: Kazuo Yamagata (Sakajiri Naika Iin), Hideki Kuribayashi (Aohitokusa Kuribayashi Clinic), Daishiro Yamada (Jiyugaoka Yamada Clinic of Internal Medicine), Fuminobu Okuguchi (Okuguchi Clinic of Internal Medicine), Hiroshi Kouno (Jusendo General Hospital), Shuichi Fukuda (Wakakusa Clinic), Hirokazu Shoda (Seiwakai Shoda Hospital), Hideto Ishii (Asano Internal Medicine Clinic, Medical Corporation Yukeikai), Tomio Tsukazaki (Aozora Total Clinic), Shinya Minagawa (Minagawa Clinic), Madoka Taguchi (Toshiba General Hospital), Katsuhiko Yamada (Kousei Medical Clinic), Masahiro Sugawara (Sugawara Clinic), Koki Shin (Shin Clinic), Yoshio Ohashi (Tokyo Ekimae-building Clinic), Takaaki Iwai (Sagamino Central Hospital), Ikuro Matsuba (Matsuba Clinic), Ichitaro Takada (Takada Internal Medicine Clinic), Mizuki Kaneshiro (Kaneshiro Diabetes Clinic), Yoichi Koizumi (Komoro Kosei General Hospital), Takuro Ichikawa (Ichikawa Clinic), Kotaro Kawai (Shimada Municipal Hospital), Naoko Hirahara (Shimada Municipal Hospital), Kiyomitsu Ikeoka (Medical Corporation Ikeoka Clinic), Sadahiro Sempuku (Senpuku Clinic), Tetsuji Okuno (Nippon Kokan Fukuyama Hospital), Yasuo Toh (Healthcare Corporations Association Kunwa-Kai Aiwa Clinic), Daigaku Uchida (Medical Corporation Hotaruno Hakuyukai), Tsuguyoshi Asano (Asano Kanamachi Clinic), Makoto Sugiura (Specified Medical Corporation Tokoharu and Touei Hospital), Tamayuki Koizumi (Medical Corporation Pieta Association Ishikari Hospital), Munenori Okamoto (Sapporo Century Hospital), Masahiko Takai (Medical Corporation Takai Internal Medicine Clinic), Yoshiyuki Arai (Arai Clinic), Masakazu Kato (Kato Internal Medicine Clinic), Kazunori Yokoyama (Nikko Memorial Hospital), Kazuo Satake (Fukui General Clinic), Yasuhiro Hashiguchi (Tenpozan Internal Clinic).

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Kashiwagi, A., Shiga, T., Akiyama, N. et al. Efficacy and safety of ipragliflozin as an add-on to pioglitazone in Japanese patients with inadequately controlled type 2 diabetes: a randomized, double-blind, placebo-controlled study (the SPOTLIGHT study). Diabetol Int 6, 104–116 (2015). https://doi.org/10.1007/s13340-014-0182-y

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