Journal of diabetes investigation 2018 04 06() doi 10.1111/jdi.12849
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.