Lege Artis Medicinae

[INCRETIN MIMETICS AND INCRETIN ENHANCERS: NEW THERAPEUTIC TOOLS IN THE TREATMENT OF PATIENTS WITH TYPE 2 DIABETES MELLITUS]

JERMENDY György

NOVEMBER 10, 2008

Lege Artis Medicinae - 2008;18(11)

[Incretins are hormone-like peptides secreted by specific cells of the small intestine mucosa. Their two main representatives are the glucagon-likepeptide- 1 (GLP-1 and the glucose-dependent insulinotropic peptide, (GIP) the release of which is stimulated by meals. The main action of incretins is to enhance insulin secretion following meals. They are rapidly metabolized in the circulation by the enzyme dipeptidyl peptidase IV (DPP-IV). Patients with type 2 diabetes have markedly impaired incretin-mediated insulin secretion mainly due to decreased secretion of GLP-1. Research in the last years has opened up a new therapeutic option to treat patients with type 2 diabetes. Continuous intravenous use of GLP-1 cannot be widely used in clinical practice; however, GLP-1-mimetics that have an agonist effect on the receptors but are resistant to degradation by DPP-IV have been developed. The GLP-1 agonist xenatide, due to its incretin mimetic property, stimulates postprandial insulin secretion, suppresses glucagon secretion, delays gastric emptying and increases sense of fullness thus resulting in weight reduction. In experimental settings, exenatide has a documented beta-cell protecting property. Its disadvantages include the fact that it can only be administered subcutaneously and that it has a well characterized side effect profile. On the contrary, the DPP-IV inhibiting incretin enhancers (sitagliptin, vildagliptin) can be used orally and are well tolerated. Exenatide, sitagliptin and vildagliptin are the first representatives of incretin mimetics and incretin enhancers. Sitagliptin has been available in Hungary since August, 2008. Their effect to reduce blood glucose and HbA1c should mainly be exploited in combination therapy, preferably with metformin. The availability of incretin mimetics and incretin enhancers will offer new therapeutic options for treating patients with type 2 diabetes. Nevertheless, the final assessment of these new drugs will require long-term experience in the clinical practice.]

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