Major Findings: Premeal exenatide injections significantly improved postprandial serum triglyceride levels and endothelial function in patients with impaired glucose tolerance or type 2 diabetes.
Source of Data: Double-blinded crossover trial of 35 patients
Disclosures: The study was funded in part by Amylin Pharmaceuticals and Lilly USA, which jointly market exenatide.
SAN FRANCISCO — A premeal injection of exenatide significantly reduced postprandial serum triglyceride levels compared with placebo in a randomized, double-blinded crossover trial in 35 patients with impaired glucose tolerance or recent-onset type 2 diabetes mellitus.
In 28 patients who also underwent endothelial function tests, postprandial endothelial function was significantly better after premeal exenatide compared with placebo, and after researchers controlled for preinjection endothelial function values, Dr. Gerald Reaven said at the Sixth Annual World Congress on the Insulin Resistance Syndrome.
Further analysis suggested that the effects on postprandial triglyceride levels explained about 60% of the effects on endothelial function, added Dr. Reaven, director of the diabetes program at the Veterans Affairs Medical Center, Phoenix.
Investigators are hoping that acute therapy with exenatide or other incretin mimetics may alter metabolic factors to favorably affect endothelial dysfunction, which occurs in the early stages of diabetes. Endothelial dysfunction has been associated with cardiovascular disease, the No. 1 cause of morbidity and mortality in patients with type 2 diabetes. More research is needed to see if acute therapy can improve endothelial function.
Exenatide injection also significantly improved postprandial serum levels of apolipoprotein B48, remnant lipoprotein cholesterol, and remnant lipoprotein triglycerides compared with placebo injection, he reported.
Twenty patients with impaired glucose tolerance and 15 with type 2 diabetes diagnosed within the past 3 years whose hemoglobin A1c levels were well controlled on diet without medication were randomized to receive a premeal subcutaneous injection of 10 mcg exenatide or saline before eating a calorically dense meal consisting of 45% fat, 40% carbohydrates, and 50% protein. After a 1- to 2-week washout period, the exenatide and saline groups switched therapies. Endothelial function was measured by peripheral arterial tonometry.