Welcome from Grazia Aleppo, MD, FACE, FACP
In this edition of EndoScan, we will focus on the beneficial effect of the glucagon-like peptide 1 (GLP-1) receptor agonists in the therapy of type 2 diabetes. We have chosen 3 recent studies that reported on this issue, and at the end of every abstract, a short commentary has been provided.
The GLP-1 receptor agonists, also called incretin mimetics, are a class of anti-hyperglycemic medications with a glucose-dependent effect on pancreatic secretion of insulin and glucagon.
The term “incretin effect” was coined to describe the response involving the stimulatory effect of gut hormones on pancreatic secretion. The naturally occurring GLP-1 and GIP (gastric-inhibiting peptide) are the “incretin” hormones and are secreted primarily from the L cells (GLP-1) located in the distal gut (ileum and colon) and from the K cells (GIP) located in the proximal gut (duodenum).
Together, they enhance the insulin response of the pancreatic beta cells to glycemic elevations. GLP-1 also suppresses overall glucagon secretion from pancreatic alpha cells when glucose levels are elevated. Additionally, GLP-1 and GIP promote satiety and decrease gastric emptying, and their use is associated with weight loss.
This class of medication includes two FDA-approved products, exenatide and liraglutide. Because of the glucose-dependent action on insulin and glucagon secretion, these medications are associated with improved glycemic control without increased risk for hypoglycemia and constitute an excellent tool for the use in the therapy of type 2 diabetes.
Take Home Messages
- Exenatide and liraglutide are well-established therapies for diabetes, and they can be used in addition to any oral medication. Exenatide can also now be used in addition to insulin.
- Their use is associated with improvement in the HbA1c without causing significant increase in hypoglycemia, and they also cause weight loss that is sustained for up to 1 year in the reported literature.
- The use of exenatide also decreases body mass fat and waist circumference in addition to reducing biomarkers of cardiovascular risks such as C-reactive protein.
- Changing from a twice daily regimen with exenatide to a once-daily regimen with liraglutide can further improve glycemic control by further decreasing of HbA1c, increasing, weight loss, and further decreasing fasting blood glucoses.
- Finally, the use of exenatide in addition to insulin causes further benefit by decreasing HbA1c, causing weight loss, and decreasing the daily insulin dose requirements.