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

Author:

Bunck Mathijs C.1,Cornér Anja23,Eliasson Bjorn4,Heine Robert J.15,Shaginian Rimma M.6,Taskinen Marja-Riitta2,Smith Ulf4,Yki-Järvinen Hannele2,Diamant Michaela1

Affiliation:

1. Diabetes Center, Department of Internal Medicine, VU University Medical Center, Amsterdam, the Netherlands

2. Department of Medicine, Helsinki University Central Hospital, Helsinki, Finland

3. Minerva Medical Research Institute, Helsinki, Finland

4. Lundberg Laboratory for Diabetes Research, Sahlgrenska University Hospital, Goteborg, Sweden

5. Eli Lilly and Company, Indianapolis, Indiana

6. Eli Lilly and Company, Houten, the Netherlands

Abstract

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, respectively; P = 0.028). CONCLUSIONS EXE and GLAR sustained HbA1c over the 3-year treatment period, while EXE reduced body weight and GLAR increased body weight. Following the 3-year treatment with EXE, the DI was sustained after a 4-week off-drug period. These findings suggest a beneficial effect on β-cell health.

Publisher

American Diabetes Association

Subject

Advanced and Specialized Nursing,Endocrinology, Diabetes and Metabolism,Internal Medicine

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