Susan Grandy, Alka Shaunik, Elise Hardy
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.