The evolving place of incretin-based therapies in type 2 diabetes

Medizinische Klinik IV, Otfried-Müller-Strasse 10, 72076, Tübingen, Germany.
Pediatric Nephrology (Impact Factor: 2.86). 07/2010; 25(7):1207-17. DOI: 10.1007/s00467-009-1435-z
Source: PubMed


Treatment options for type 2 diabetes based on the action of the incretin hormone glucagon-like peptide-1 (GLP-1) were first introduced in 2005. These comprise the injectable GLP-1 receptor agonists solely acting on the GLP-1 receptor on the one hand and orally active dipeptidyl-peptidase inhibitors (DPP-4 inhibitors) raising endogenous GLP-1 and other hormone levels by inhibiting the degrading enzyme DPP-4. In adult medicine, both treatment options are attractive and more commonly used because of their action and safety profile. The incretin-based therapies stimulate insulin secretion and inhibit glucagon secretion in a glucose-dependent manner and carry no intrinsic risk of hypoglycaemia. GLP-1 receptor agonists allow weight loss, whereas DPP-4 inhibitors are weight neutral. This review gives an overview of the mechanism of action and the substances and clinical data available.

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    • "The resulting agonists and antagonists have increased metabolic stability, biological activity, and bioavailability. For example, the energy metabolism-regulating hormone Glp1 is highly unstable with a bioavailability of only 1–2 min due to its rapid enzymatic degradation by dipeptidyl peptidase 4. In contrast, the N-acylated Glp1 analog Liraglutide has a half life of 14 h, which makes it suitable for the treatment of type 2 diabetes73. Exenatide, an analog of the naturally occurring Glp1 agonist Exendin-4, in which the second alanine is substituted by serine, improves both stability and activity73. "
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