The Singapore Family Physician

Back to issue Vol 37 No. 4 - Cardiometabolic Risk Update

How Do Incretin-Based Therapies Fit Into the Treatment Algorithm?

Chia Su-Ynn
The Singapore Family Physician Vol 37 No 4 - Cardiometabolic Risk Update
25 - 28
1 October 2011
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), termed “incretins,” are gut-derived peptide hormones released from intestinal K and L cells into the bloodstream in response to ingested nutrients. They greatly augment the insulin response of the pancreas to an oral glucose load. In patients with T2DM, particularly those with more long standing disease and poorer glycemic control (HbA1c ∼8–9%), the GLP-1 response to glucose and mixed meal challenges is decreased, but GIP secretion is unchanged when compared to healthy subjects. Also, acute GLP-1 administration is able to increase insulin secretion to normal levels and to lower plasma glucose effectively in these patients. The main drawback with GLP-1 is its short half-life (∼1–2 min for the intact, biologically active form). For this reason, GLP-1 analogues, also known as “incretin mimetics” (e.g., exenatide and liraglutide) with considerably longer half-lives were developed. All incretin mimetics are peptides and need to be administered by subcutaneous injection. Exenatide has a half-life of ∼3 h and has been approved for administration (twice-daily injections) to type 2 diabetic patients inadequately controlled by oral antidiabetic agent, and lowers Hb A1c by about 0.7-1%. Liraglutide has a half-life of 12–14 h (suitable for once-daily administration) and can lower HbA1c between 1-1.5%. GLP-1 analogues provoke significant weight loss, which is especially important when considered against the weight gain associated with, e.g., sulfonylureas, TZDs, and insulin. Based on these advantages, incretin-based therapies have been mentioned in recent treatment algorithms for the treatment of type 2 diabetes.