G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients
Abstract Aims/Introduction Pancreatic β‐cell dysfunction contributes to type 2 diabetes mellitus progression. Drugs that improve insulin secretion might be a valuable treatment approach. The present study aimed to evaluate the effect of the G protein‐coupled receptor 119 agonist DS‐8500a on insulin...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Journal of Diabetes Investigation |
| Subjects: | |
| Online Access: | https://doi.org/10.1111/jdi.12849 |
| _version_ | 1819296660354760704 |
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| author | Hirotaka Watada Masanari Shiramoto Shin Irie Yasuo Terauchi Yuichiro Yamada Kazuhito Shiosakai Yusuke Myobatake Takashi Taguchi |
| author_facet | Hirotaka Watada Masanari Shiramoto Shin Irie Yasuo Terauchi Yuichiro Yamada Kazuhito Shiosakai Yusuke Myobatake Takashi Taguchi |
| author_sort | Hirotaka Watada |
| collection | DOAJ |
| description | Abstract Aims/Introduction Pancreatic β‐cell dysfunction contributes to type 2 diabetes mellitus progression. Drugs that improve insulin secretion might be a valuable treatment approach. The present study aimed to evaluate the effect of the G protein‐coupled receptor 119 agonist DS‐8500a on insulin secretory capacity in Japanese type 2 diabetes mellitus patients. Materials and Methods This single‐center, 4‐week, randomized, double‐blind, cross‐over study enrolled 21 Japanese drug‐naïve type 2 diabetes mellitus patients aged ≥20 years with glycated hemoglobin ≥7.0 and <9.0% (NCT02669732, JapicCTI 163126). Patients received 75 mg of DS‐8500a or a placebo orally daily for 4 weeks in a random order. A combined euglycemic‐hyperinsulinemic and hyperglycemic clamp test was carried out to assess insulin secretion and insulin sensitivity before and after each 4‐week treatment period. Primary end‐points were first‐phase insulin secretion (insulin area under the curve [AUC]180–190 min and C‐peptide AUC180–190 min during the clamp test) and second‐phase insulin secretion (insulin AUC190–300 min and C‐peptide AUC190–300 min). Insulin sensitivity (M and M/I values), disposition index and changes in lipid profile were also assessed. Results DS‐8500a significantly increased first‐ and second‐phase insulin AUC (P = 0.0011, P = 0.0112) and C‐peptide AUC (P = 0.0012, P < 0.0001) compared with the placebo. At day 28, M and M/I values were comparable with those of the placebo, whereas the disposition index for insulin and C‐peptide was significantly increased (P = 0.0108, P = 0.0002). Total cholesterol, low‐density lipoprotein cholesterol and triglyceride concentrations were significantly reduced, and high‐density lipoprotein cholesterol concentrations were significantly increased compared with the placebo. No significant treatment‐emergent adverse events occurred. Conclusion DS‐8500a enhanced insulin secretory capacity, but not insulin sensitivity. |
| first_indexed | 2024-12-24T05:01:38Z |
| format | Article |
| id | doaj.art-0162078a8f384a54981915c232e5854b |
| institution | Directory Open Access Journal |
| issn | 2040-1116 2040-1124 |
| language | English |
| last_indexed | 2024-12-24T05:01:38Z |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Investigation |
| spelling | doaj.art-0162078a8f384a54981915c232e5854b2022-12-21T17:14:00ZengWileyJournal of Diabetes Investigation2040-11162040-11242019-01-01101849310.1111/jdi.12849G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patientsHirotaka Watada0Masanari Shiramoto1Shin Irie2Yasuo Terauchi3Yuichiro Yamada4Kazuhito Shiosakai5Yusuke Myobatake6Takashi Taguchi7Department of Metabolism and Endocrinology Juntendo University Graduate School of Medicine Tokyo JapanSOUSEIKAI Hakata Clinic Hakata Fukuoka JapanSOUSEIKAI Hakata Clinic Hakata Fukuoka JapanDepartment of Endocrinology and Metabolism Yokohama City University Graduate School of Medicine Yokohama Kanagawa JapanDepartment of Endocrinology, Diabetes and Geriatric Medicine Akita University School of Medicine Akita JapanBiostatistics & Data Management Daiichi Sankyo Co., Ltd Tokyo JapanClinical Development Department, Daiichi Sankyo Co., Ltd Tokyo JapanClinical Development Department, Daiichi Sankyo Co., Ltd Tokyo JapanAbstract Aims/Introduction Pancreatic β‐cell dysfunction contributes to type 2 diabetes mellitus progression. Drugs that improve insulin secretion might be a valuable treatment approach. The present study aimed to evaluate the effect of the G protein‐coupled receptor 119 agonist DS‐8500a on insulin secretory capacity in Japanese type 2 diabetes mellitus patients. Materials and Methods This single‐center, 4‐week, randomized, double‐blind, cross‐over study enrolled 21 Japanese drug‐naïve type 2 diabetes mellitus patients aged ≥20 years with glycated hemoglobin ≥7.0 and <9.0% (NCT02669732, JapicCTI 163126). Patients received 75 mg of DS‐8500a or a placebo orally daily for 4 weeks in a random order. A combined euglycemic‐hyperinsulinemic and hyperglycemic clamp test was carried out to assess insulin secretion and insulin sensitivity before and after each 4‐week treatment period. Primary end‐points were first‐phase insulin secretion (insulin area under the curve [AUC]180–190 min and C‐peptide AUC180–190 min during the clamp test) and second‐phase insulin secretion (insulin AUC190–300 min and C‐peptide AUC190–300 min). Insulin sensitivity (M and M/I values), disposition index and changes in lipid profile were also assessed. Results DS‐8500a significantly increased first‐ and second‐phase insulin AUC (P = 0.0011, P = 0.0112) and C‐peptide AUC (P = 0.0012, P < 0.0001) compared with the placebo. At day 28, M and M/I values were comparable with those of the placebo, whereas the disposition index for insulin and C‐peptide was significantly increased (P = 0.0108, P = 0.0002). Total cholesterol, low‐density lipoprotein cholesterol and triglyceride concentrations were significantly reduced, and high‐density lipoprotein cholesterol concentrations were significantly increased compared with the placebo. No significant treatment‐emergent adverse events occurred. Conclusion DS‐8500a enhanced insulin secretory capacity, but not insulin sensitivity.https://doi.org/10.1111/jdi.12849Diabetes mellitusHyperglycemic clampPancreatic β‐cells |
| spellingShingle | Hirotaka Watada Masanari Shiramoto Shin Irie Yasuo Terauchi Yuichiro Yamada Kazuhito Shiosakai Yusuke Myobatake Takashi Taguchi G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients Journal of Diabetes Investigation Diabetes mellitus Hyperglycemic clamp Pancreatic β‐cells |
| title | G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients |
| title_full | G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients |
| title_fullStr | G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients |
| title_full_unstemmed | G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients |
| title_short | G protein‐coupled receptor 119 agonist DS‐8500a effects on pancreatic β‐cells in Japanese type 2 diabetes mellitus patients |
| title_sort | g protein coupled receptor 119 agonist ds 8500a effects on pancreatic β cells in japanese type 2 diabetes mellitus patients |
| topic | Diabetes mellitus Hyperglycemic clamp Pancreatic β‐cells |
| url | https://doi.org/10.1111/jdi.12849 |
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