Effects of Exenatide on Measures of β-Cell Function After 3 Years in Metformin-Treated Patients With Type 2 Diabetes

作者：Mathijs C. M. Bunck, A. H. Corner, Björn Eliasson, Robert J. Heine, Rimma M. Shaginian, Marja‐Riitta Taskinen, Ulf Smith, Hannele Yki‐Järvinen, Michaëla Diamant · 发表于：Diabetes Care · 年份：2011 · DOI：10.2337/dc11-0291 · 被引用次数：240 · 研究领域：Diabetes Treatment and Management、Diabetes, Cardiovascular Risks, and Lipoproteins、Pancreatic function and diabetes

OBJECTIVE: We previously showed that exenatide (EXE) enhanced insulin secretion after 1 year of treatment, relative to insulin glargine (GLAR), with a similar glucose-lowering action. These effects were not sustained after a 4-week off-drug period. This article reports the results after additional 2 years of exposure. RESEARCH DESIGN AND METHODS: Sixty-nine metformin-treated patients with type 2 diabetes were randomized to EXE or GLAR. Forty-six patients entered the 2-year extension study in which they continued their allocated therapy. Thirty-six completed (EXE: n = 16; GLAR: n = 20) the 3-year exposure period. Insulin sensitivity (M value) and β-cell function were measured by euglycemic hyperinsulinemic clamp followed by hyperglycemic clamp with arginine stimulation at pretreatment (week 52) and 4 weeks after discontinuation of study medication (week 56 and week 172). First-phase glucose stimulated C-peptide secretion was adjusted for M value and calculated as the disposition index (DI). RESULTS: At 3 years, EXE and GLAR resulted in similar levels of glycemic control: 6.6 ± 0.2% and 6.9 ± 0.2%, respectively (P = 0.186). EXE compared with GLAR significantly reduced body weight (-7.9 ± 1.8 kg; P < 0.001). After the 4-week off-drug period, EXE increased the M value by 39% (P = 0.006) while GLAR had no effect (P = 0.647). Following the 4-week off-drug period, the DI, compared with pretreatment, increased with EXE, but decreased with GLAR (1.43 ± 0.78 and -0.99 ± 0.65, respectiv...