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Review
. 2006 Nov 11;368(9548):1696-705.
doi: 10.1016/S0140-6736(06)69705-5.

The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes

Daniel J Drucker  1 , Michael A Nauck
Affiliations
Review

The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes

Daniel J Drucker et al. Lancet. .

Abstract

Glucagon-like peptide 1 (GLP-1) is a gut-derived incretin hormone that stimulates insulin and suppresses glucagon secretion, inhibits gastric emptying, and reduces appetite and food intake. Therapeutic approaches for enhancing incretin action include degradation-resistant GLP-1 receptor agonists (incretin mimetics), and inhibitors of dipeptidyl peptidase-4 (DPP-4) activity (incretin enhancers). Clinical trials with the incretin mimetic exenatide (two injections per day or long-acting release form once weekly) and liraglutide (one injection per day) show reductions in fasting and postprandial glucose concentrations, and haemoglobin A1c (HbA1c) (1-2%), associated with weight loss (2-5 kg). The most common adverse event associated with GLP-1 receptor agonists is mild nausea, which lessens over time. Orally administered DPP-4 inhibitors, such as sitagliptin and vildagliptin, reduce HbA1c by 0.5-1.0%, with few adverse events and no weight gain. These new classes of antidiabetic agents, and incretin mimetics and enhancers, also expand beta-cell mass in preclinical studies. However, long-term clinical studies are needed to determine the benefits of targeting the incretin axis for the treatment of type 2 diabetes.

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Comment in

  • Gliptins.
    Mikhail N. Mikhail N. Lancet. 2007 Jan 27;369(9558):269. doi: 10.1016/S0140-6736(07)60136-6. Lancet. 2007. PMID: 17258655 No abstract available.
  • Gliptins.
    Focosi D, Kast RE, Petrini M. Focosi D, et al. Lancet. 2007 Jan 27;369(9558):269-70. doi: 10.1016/S0140-6736(07)60137-8. Lancet. 2007. PMID: 17258656 No abstract available.
  • Gliptins.
    Grouzmann E, Buclin T, Biollaz J. Grouzmann E, et al. Lancet. 2007 Jan 27;369(9558):269. doi: 10.1016/S0140-6736(07)60135-4. Lancet. 2007. PMID: 17258657 No abstract available.

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