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