Pathogenesis and Management of Postprandial Hyperglycemia: Role of Incretin-based Therapies

Postprandial plasma glucose concentrations are an important contributor to glycemic control. There is evidence suggesting that postprandial hyperglycemia may be an independent risk factor for cardiovascular disease. Glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are antidiabetic agents that predominantly reduce postprandial plasma glucose levels. DPP-4 inhibitors are associated with fewer gastrointestinal side effects than GLP-1 receptor agonists and are administered orally, unlike GLP-1 analogs, which are administered as subcutaneous injections. GLP-1 receptor agonists are somewhat more effective than DPP-4 inhibitors in reducing postprandial plasma glucose and are usually associated with significant weight loss. For these reasons, GLP-1 receptor agonists are generally preferred over DPP-4 inhibitors as part of combination treatment regimens in patients with glycated hemoglobin levels above 8.0%. This article reviews the pathogenesis of postprandial hyperglycemia, the mechanisms by which GLP-1 receptor agonists and DPP-4 inhibitors reduce postprandial plasma glucose concentrations, and the results of recent clinical trials (ie, published 2008 to October 2012) that evaluated the effects of these agents on postprandial plasma glucose levels when evaluated as monotherapy compared with placebo or as add-on therapy to metformin, a sulfonylurea, or insulin. Findings from recent clinical studies suggest that both GLP-1 receptor agonists and DPP-4 inhibitors could become valuable treatment options for optimizing glycemic control in patients unable to achieve glycated hemoglobin goals on basal insulin, with the added benefits of weight loss and a low risk of hypoglycemia.