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Exploiting the antidiabetic properties of physiologic incretins to treat type 2 diabetes mellitus: exenatide or insulin for patients with inadequate glycemic control using oral antidiabetic agents?

L Van Gaal, Endocrinology and Diabetology, Antwerp University Hospital , Antwerp, 2650, Belgium
S Gutkin, Rete Biomedical Communications Corp., Ridgewood, United States
M Nauck, Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany

Correspondence: Lf Van Gaal, Email: luc.van.gaal{at}uza.be

Abstract

Type 2 diabetes mellitus is associated with progressive decreases in pancreatic beta*-cell function. Most patients thus require increasingly intensive treatment, including combination oral therapies followed by insulin. Fear of hypoglycemia is a potential barrier to treatment adherence and glycemic control, while weight gain can exacerbate hyperglycemia or insulin resistance. Administration of insulin can roughly mimic physiologic insulin secretion but does not address underlying pathophysiology. Glucagon-like peptide-1 (GLP-1) is an incretin hormone released by the gut in response to meal intake that helps to maintain glucose homeostasis through coordinated effects on islet - and β-cells, inhibiting glucagon output and stimulating insulin secretion in a glucose-dependent manner. Biological effects of GLP-1 include slowing gastric emptying and decreasing appetite. Incretin mimetics (GLP-1 receptor agonists with more suitable pharmacokinetic properties vs GLP-1) significantly lower hemoglobin A1c, body weight, and postprandial glucose excursions in humans and significantly improve β-cell function in vivo (animal data). These novel incretin-based therapies offer the potential to reduce body weight or prevent weight gain, although the durability of these effects and their potential long-term benefits need to be studied further. This article reviews recent clinical trials comparing therapy with the incretin mimetic exenatide to insulin in patients with oral treatment failure; identifies factors consistent with the use of each treatment; and delineates areas for future research.