Send to

Choose Destination
See comment in PubMed Commons below
Rev Diabet Stud. 2005 Summer;2(2):61-9. Epub 2005 Aug 10.

New therapeutic strategies for the treatment of type 2 diabetes mellitus based on incretins.

Author information

  • 1Department of Medicine IV, Eberhard-Karls-University, Otfried-Müller-Strasse 10, 72076 Tübingen, Germany.


Orally ingested glucose leads to a greater insulin response compared to intravenously administered glucose leading to identical postprandial plasma glucose excursions, a phenomenon referred to as the "incretin effect". The incretin effect comprises up to 60% of the postprandial insulin secretion and is diminished in type 2 diabetes. One of the very important gastrointestinal hormones promoting this effect is glucagon-like peptide 1 (GLP-1). It only stimulates insulin secretion and normalizes blood glucose in humans under hyperglycemic conditions, therefore it does not cause hypoglycemia. Other important physiological actions of GLP-1 are the inhibition of glucagon secretion and gastric emptying. It further acts as a neurotransmitter in the hypothalamus stimulating satiety. In vitro and animal data demonstrated that GLP-1 increases beta-cell mass by stimulating islet cell neogenesis and by inhibiting apoptosis of islets. In humans, the improvement of beta-cell function can be indirectly observed from the increased insulin secretory capacity after GLP-1 infusions. GLP-1 represents an attractive therapeutic principle for type 2 diabetes. However, native GLP-1 is degraded rapidly upon exogenous administration and is therefore not feasible for routine therapy. The first long-acting GLP-1 analog ("incretin mimetic") Exenatide (Byetta) has just been approved for type 2 diabetes therapy. Other compounds are being investigated in clinical trials (e.g. liraglutide, CJC1131). Dipeptidyl-peptidase IV inhibitors (DPP-IV inhibitors; e.g. Vildagliptin, Sitagliptin) that inhibit the enzyme responsible for incretin degradation are also under study.

PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Society for Biomedical Diabetes Research Icon for PubMed Central
    Loading ...
    Support Center