Lancet (London, England)Nov 14, 2006

The incretin system: treatments targeting hormone receptors and enzymes in type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

Clinical trials show reductions in haemoglobin A1c (HbA1c) of 1-2% with incretin mimetics and 0.5-1.0% with DPP-4 inhibitors.

GLP-1 is a hormone that promotes insulin release and reduces appetite.
Incretin mimetics, such as exenatide and liraglutide, are effective in lowering fasting and postprandial glucose levels.
Weight loss of 2-5 kg is associated with the use of GLP-1 receptor agonists.
Common side effects of GLP-1 receptor agonists include mild nausea, which typically decreases over time.
Oral DPP-4 inhibitors like sitagliptin and vildagliptin have minimal side effects and do not lead to weight gain.
Preclinical studies suggest these antidiabetic agents may help increase beta-cell mass.

Simplified

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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The incretin system: treatments targeting hormone receptors and enzymes in type 2 diabetes

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