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GPR119 Agonist DS-8500a Effects on Pancreatic β-Cells in Japanese Type 2 Diabetes Mellitus Patients.

GPR119 Agonist DS-8500a Effects on Pancreatic β-Cells in Japanese Type 2 Diabetes Mellitus Patients.
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Watada H, Shiramoto M, Irie S, Terauchi Y, Yamada Y, Shiosakai K, Myobatake Y, Taguchi T,


Watada H, Shiramoto M, Irie S, Terauchi Y, Yamada Y, Shiosakai K, Myobatake Y, Taguchi T, (click to view)

Watada H, Shiramoto M, Irie S, Terauchi Y, Yamada Y, Shiosakai K, Myobatake Y, Taguchi T,

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Journal of diabetes investigation 2018 04 06() doi 10.1111/jdi.12849
Abstract
INTRODUCTION
Pancreatic β-cell dysfunction contributes to type 2 diabetes mellitus (T2DM) progression. Drugs that improve insulin secretion may be a valuable treatment approach. This study aimed to evaluate the effect of the G protein-coupled receptor 119 agonist DS-8500a on insulin secretory capacity in Japanese T2DM patients.

MATERIALS AND METHODS
This single-center, 4-week, randomized, double-blind, crossover study enrolled 21 Japanese drug-naïve T2DM patients aged ≥20 years with glycated hemoglobin ≥7.0% and <9.0% (NCT02669732, JapicCTI 163126). Patients received 75 mg of DS-8500a or placebo orally daily for 4 weeks in a random order. A combined euglycemic-hyperinsulinemic and hyperglycemic clamp test was performed to assess insulin secretion and insulin sensitivity before and after each 4-week treatment period. Primary endpoints were first-phase insulin secretion (insulin area under the curve [AUC]and C-peptide AUCduring the clamp test) and second-phase insulin secretion (insulin AUCand C-peptide AUC). Insulin sensitivity (M and M/I values), disposition index (DI), 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 placebo. At Day 28, M and M/I values were comparable to those of placebo, while the DI 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 placebo. No significant treatment-emergent adverse events occurred. DISCUSSION
DS-8500a enhanced insulin secretory capacity but not insulin sensitivity. This article is protected by copyright. All rights reserved.

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