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Glucose-lowering effects and safety of DS-8500a, a G protein-coupled receptor 119 agonist, in Japanese patients with type 2 diabetes: results of a randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase II study
  1. Nobuya Inagaki1,
  2. Hubert S Chou2,
  3. Shuji Tsukiyama3,
  4. Takuo Washio4,
  5. Kazuhito Shiosakai5,
  6. Yasuhiko Nakatsuka6,
  7. Takashi Taguchi6
  1. 1Department of Diabetes, Endocrinology and Nutrition, Kyoto University Graduate School of Medicine, Kyoto, Japan
  2. 2Clincal Development Department, Daiichi SankyoPharma Development, Daiichi Sankyo Pharma Development, Edison, New Jersey, USA
  3. 3Development Planning Department, Daiichi Sankyo Development, Buckinghamshire, UK
  4. 4Asia Development Department, Daiichi Sankyo, Tokyo, Japan
  5. 5Biostatistics & Data Management Department, Daiichi Sankyo, Tokyo, Japan
  6. 6Clinical Development Department, Daiichi Sankyo, Tokyo, Japan
  1. Correspondence to Dr Takashi Taguchi; taguchi.takashi.ft{at}daiichisankyo.co.jp

Abstract

Objective DS-8500a is a novel G protein-coupled receptor 119 agonist being developed for the treatment of type 2 diabetes. The study objective was to assess the efficacy and safety of DS-8500a in Japanese patients with type 2 diabetes.

Research design and methods In this double-blind, parallel-group, phase II study, 99 Japanese patients with type 2 diabetes were randomized to receive placebo, or DS-8500a 10 mg or 75 mg once daily for 28 days. The primary efficacy endpoint was change in the 24-hour weighted mean glucose (WMG) from baseline (day −1) to day 28. Other endpoints included changes in fasting plasma glucose, postprandial glucose, lipids, and safety.

Results The 24-hour WMG decreased significantly after 28 days of treatment in the 10 mg and 75 mg groups with placebo-subtracted least squares mean differences (95% CI) of −0.74 (−1.29 to –0.19) mmol/L and −1.05 (−1.59 to –0.50) mmol/L, respectively. Reductions in 24-hour WMG in both DS-8500a groups were observed on day 14 and were greater on day 28 than on day 14. The reductions in fasting plasma glucose and 2-hour postprandial glucose were significantly greater in the 75 mg DS-8500a group versus placebo. Total cholesterol, low-density lipoprotein cholesterol, and triglycerides decreased significantly; high-density lipoprotein cholesterol increased significantly in the 75 mg group versus placebo. Both doses of DS-8500a were well tolerated without significant treatment-related adverse events, hypoglycemia, or discontinuations due to adverse events.

Conclusions DS-8500a significantly improved glycemic control and lipids and was well tolerated over 28 days of administration in Japanese patients with type 2 diabetes.

Trial registration number NCT02222350; Post-results.

  • G protein-coupled receptor 119 agonist
  • glycemic control
  • Japanese
  • phase II clinical trial
  • type 2 diabetes

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Footnotes

  • Contributors NI, HSC, ST, TW, KS, YN, and TT contributed to study design, data analysis, and writing of the manuscript. As corresponding author, TT is guarantor for the content of this article.

  • Funding Medical writing support was provided by Nicholas D Smith, PhD (Edanz Medical Writing) and was funded by Daiichi Sankyo.

  • Competing interests NI has acted as a consultant for Novo Nordisk and Arkray Marketing; has received research support from Kissei Pharmaceutical, Eli Lilly Japan KK, Novartis Pharma KK, Daiichi Sankyo, Sanofi KK, Pfizer Japan, Mitsubishi Tanabe Pharma Corporation, Takeda Pharmaceutical Company, Japan Tobacco, Kyowa Hakko Kirin, Dainippon Sumitomo Pharma, Astellas Pharma, Merck Sharp & Dohme, Sanwa Kagaku Kenkyusho, Boehringer Ingelheim Japan, Ono Pharmaceutical, Tsumura & Co, Fujifilm Pharma, Shiratori Pharmaceutical, and Taisho Toyama Pharmaceutical; has served on the speaker’s bureau for Merck Sharp & Dohme, Astellas Pharma, Eisai, Sanofi KK, Novo Nordisk, Kowa Pharmaceutical, Ono Pharmaceutical, Dainippon Sumitomo Pharma, Daiichi Sankyo, Eli Lilly Japan KK, Boehringer Ingelheim Japan, Arkray Marketing, Japan Tobacco, Takeda Pharmaceutical Company, and Johnson & Johnson; and has acted as the medical adviser on a clinical trial performed by Daiichi-Sankyo. HSC is an employee of Daiichi Sankyo Pharma Development. ST is an employee of Daiichi Sankyo Development. TW, KS, YN, and TT are employees of Daiichi Sankyo.

  • Ethics approval IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement No additional information is available.