Effects of Glucagon-Like Peptide-1 Receptor Agonists on ÃÂ²-Cell Function in Patients with Type 2 DiabetesSusan Grandy*, Alka Shaunik and Elise Hardy
AstraZeneca, Gaithersburg, Maryland, USA
- *Corresponding Author:
- Susan Grandy
Global Medicines Development
AstraZeneca, One MedImmune Way
Gaithersburg, MD 20878, USA
Received date: January 08, 2016; Accepted date: January 23, 2016; Published date: January 30, 2016
Citation: Grandy S, Shaunik A, Hardy E (2016) Effects of Glucagon-Like Peptide-1 Receptor Agonists on β-Cell Function in Patients with Type 2 Diabetes. J Diabetes Metab 7:643. doi: 10.4172/2155-6156.1000643
Copyright: © 2016 Grandy S, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Type 2 diabetes (T2D) is characterized by insulin resistance and a progressive decline in pancreatic β-cell function. Over time, upregulation of insulin secretion is no longer sufficient to compensate for insulin resistance, leading to fasting hyperglycemia, while β-cell function continues to deteriorate. Effective treatments targeting the underlying pathophysiology of T2D involve early lifestyle interventions and a combination of therapies to counteract insulin resistance and progressive deterioration of β cells. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are one class of antihyperglycemic agents that target multiple pathways, mediating clinical benefits for patients with T2D. This review summarizes the effects of treatment with various GLP-1RAs, including exenatide (twice daily and once weekly), liraglutide, dulaglutide, and lixisenatide, on β-cell function in patients with T2D. β-cell function was assessed in randomized controlled trials and their extension studies using a variety of methods, including glucose and arginine clamp techniques, proinsulin-to-insulin ratio, and homeostatic model assessment of β-cell function (HOMA-B). Exenatide twice daily and liraglutide both improved first- and second-phase insulin secretory responses. In addition, numerous studies reported significant improvements in HOMA-B with exenatide (twice daily and once weekly; range of relative change from baseline: +28–50%; range of absolute change: +5–40%) or liraglutide (range of change vs. placebo: +13–43%). Improvements in HOMA-B were also observed with the newer GLP-1RAs dulaglutide and lixisenatide. In contrast to the effects on HOMA-B, treatment with GLP-1RAs had a lesser effect on insulin sensitivity. Taken together, the results suggest that glucagon-like peptide-1 analogs have a greater effect on β-cell function than insulin sensitivity.