Exenatide improves diastolic function and attenuates arterial stiffness but does not alter exercise capacity in individuals with type 2 diabetes

Abstract Background Exercise is recommended as a cornerstone of treatment for type 2 diabetes mellitus (T2DM), however, it is often poorly adopted by patients. Even in the absence of apparent cardiovascular disease, persons with T2DM have an impaired ability to carry out maximal and submaximal exercise and these impairments are correlated with cardiac and endothelial dysfunction. Glucagon-like pepetide-1 (GLP-1) augments endothelial and cardiac function in T2DM. We hypothesized that administration of a GLP-1 agonist (exenatide) would improve exercise capacity in T2DM. Methods and results Twenty-three participants (64 ± 4 years; mean ± SE) with uncomplicated T2DM were randomized in a double-blinded manner to receive either 10 μg BID of exenatide or matching placebo after baseline measurements. Treatment with exenatide did not improve VO 2peak (P = 0.1464) or VO 2 kinetics (P = 0.2775). Diastolic function, assessed via resting lateral E:E’, was improved with administration of exenatide compared with placebo (Placebo Pre: 7.6 ± 1.0 vs. Post: 8.4 ± 1.2 vs. Exenatide Pre: 8.1 ± 0.7 vs. Post: 6.7 ± 0.6; P = 0.0127). Additionally, arterial stiffness measured by pulse wave velocity, was reduced with exenatide treatment compared with placebo (Placebo Pre: 10.5 ± 0.8 vs. Post: 11.5 ± 1.1 s vs. Exenatide Pre: 11.4 ± 1.8 vs. Post: 10.2 ± 1.4 s; P = 0.0373). Exenatide treatment did not improve endothelial function (P = 0.1793). Conclusions Administration of exenatide improved cardiac function and reduced arterial stiffness, however, these changes were not accompanied by improved functional exercise capacity. In order to realize the benefits of this drug on exercise capacity, combining exenatide with aerobic exercise training in participants with T2DM may be warranted.