Titre du document / Document title

Mathematical modeling shows exenatide improved β-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea

Auteur(s) / Author(s)

MARI A. ; NIELSEN L. L. ; NANAYAKKARA N. ; DEFRONZO R. A. ; FERRANNINI E. ; HALSETH A. ;

Résumé / Abstract

The incretin mimetic exenatide improved glycemic control and reduced body weight in patients with type 2 diabetes inadequately controlled with metformin ± a sulfonylurea. We assessed postprandial β-cell function by mathematical modeling, independent of confounding effects from differing ambient glucose levels among treatments. Subjects were 63 % males, 55 ± 10 years, BMI 33 ± 6 kg/m², HbA_1C 8.1 ±1.1 % (± SD) randomized to 5 μg exenatide or placebo twice daily for 4 weeks. Subsequently, one arm remained at 5 μg twice daily, one arm escalated to 10 μg twice daily, and one treatment arm remained on placebo for 26 weeks. Subjects continued metformin ± a sulfonylurea. A subset with meal tests at baseline and week 30 were analyzed (n = 73). Outcome measures were the model-based β-cell function parameters dose-response relating insulin secretion to glucose concentration, rate sensitivity, and potentiation. Exenatide reduced postprandial glucose excursions. Modeling predicted an upward shift of the β-cell dose-response. Model-predicted insulin secretion rate at a reference glucose concentration increased 72% (10 μg), increased 40% (5 μg), or decreased 21% (placebo) at week 30 [p = 0.015 (10 μg); p = 0.045 (5 μg); vs. placebo]. At week 30,the 2-hour post-meal to basal potentiation factor ratio was increased to 1.53±0.10 (10 μg; p=0.0142 vs. placebo) or 1.40±0.08 (5 μg; p = 0.0402 vs. placebo) compared with 1.15±0.06 (placebo). Exenatide caused an upward shift of the p-cell dose-response and enhanced potentiation of insulin secretion. This model suggests exenatide improved p-cell function in patients with type 2 diabetes treated with metformin ± a sulfonylurea.

Revue / Journal Title

Hormone and metabolic research   ISSN 0018-5043   CODEN HMMRA2 

Source / Source

2006, vol. 38, n^o12, pp. 838-844 [7 page(s) (article)]

Langue / Language

Anglais

Editeur / Publisher

Thieme, Stuttgart, ALLEMAGNE  (1969) (Revue)

Mots-clés d'auteur / Author Keywords

Exendin-4 ; AC2993, β-cell function, insulin secretion ; incretin mimetic ; incretin potentiation ; BYETTA® BYETTA® is a registered trademark of Amylin Pharmaceuticals, Inc ;

Localisation / Location

INIST-CNRS, Cote INIST : 14356, 35400015971451.0120