Authors: Aaboe, Kasper; Krarup, Thure¹; Madsbad, Sten²; Holst, Jens Juul

Source: Diabetes, Obesity and Metabolism, Volume 10, Number 11, November 2008 , pp. 994-1003(10)

Publisher: Wiley-Blackwell

Abstract:

Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone with the potential to change diabetes. The physiological effects of GLP-1 are multiple, and many seem to ameliorate the different conditions defining the diverse physiopathology seen in type 2 diabetes. In animal studies, GLP-1 stimulates β-cell proliferation and neogenesis and inhibits β-cell apoptosis. In humans, GLP-1 stimulates insulin secretion and inhibits glucagon and gastrointestinal secretions and motility. It enhances satiety and reduces food intake and has beneficial effects on cardiovascular function and endothelial dysfunction. Enhancing incretin action for therapeutic use includes GLP-1 receptor agonists resistant to degradation (incretin mimetics) and dipeptidyl peptidase (DPP)-4 inhibitors. In clinical trials with type 2 diabetic patients on various oral antidiabetic regimes, both treatment modalities efficaciously improve glycaemic control and β-cell function. Whereas the incretin mimetics induce weight loss, the DPP-4 inhibitors are considered weight neutral. In type 1 diabetes, treatment with GLP-1 shows promising effects. However, several areas need clinical confirmation: the durability of the weight loss, the ability to preserve functional β-cell mass and the applicability in other than type 2 diabetes. As such, long-term studies and studies with cardiovascular end-points are needed to confirm the true benefits of these new classes of antidiabetic drugs in the treatment of diabetes mellitus.

Keywords: dipeptidyl peptidase 4; DPP-4 inhibitor; GLP-1; glucagon-like peptide 1; incretin effect; incretin mimetics; type 2 diabetes

Document Type: Research article

DOI: http://dx.doi.org/10.1111/j.1463-1326.2008.00853.x

Affiliations: 1: Department of Internal Medicine F, Gentofte University Hospital, Hellerup, Denmark 2: Department of Endocrinology, Hvidovre University Hospital, Hvidovre, Denmark

Publication date: 2008-11-01

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