Acute and Long-term Effects of Saxagliptin on a Set of Cardiovascular Targets Measured at Fasting and Post-prandially in Obese Patients With Impaired Glucose Tolerance: a Randomized, Placebo-controlled, Double-blind Study

Abstract Background: Studies of dipeptidyl peptidase inhibitors (DPP4is) report heterogeneous effects on cardiovascular targets in type 2 diabetes. Little is known about the cardiovascular effects of DPP4is in patients with impaired glucose tolerance (IGT) in particular during the post-prandial state. Methods: In this randomized, placebo-controlled, double-blind, single-center pilot study, we included obese individuals with IGT. Participants were randomized to receive for 12 weeks either saxagliptin 5mg a day or placebo. They were explored non-invasively before and after a standardized breakfast for biological markers; microcirculatory blood flow at baseline and after transcutaneous administration of acetylcholine (Periflux System 5000® PERIMED); post-occlusive digital reactive hyperhemia (Endopat2000®); pulse wave velocity, augmentation index, central pulse pressure and subendocardial viability ratio (Sphygmocor®); cardiac hemodynamic parameters and cardiovascular autonomic nervous system activity (Task force monitor®). Results: We investigated 24 individuals (mean body mass index 36.8±4.8 kg/m2, hypertension 33.3%). The results of all the investigations were similar after breakfast in the two groups at Visit 1 (acute post-prandial effects, after the first tablet) and Visit 2 (long-term post-prandial effects), and at fasting at Visit 1 and 2 (long-term effects, after 12 weeks of treatment). Only at Visit 2 the decrease in cardiac vagal activity occurring after breakfast was more sustained in the saxagliptin group than in the placebo group (interaction between treatment and time effect: p=0.016).Conclusion: In obese patients with IGT, among the large set of cardiovascular parameters we measured in the fasting and post-prandial state, the unique change induced by saxagliptin consisted in a more marked post-prandial depression of vagal activity. Clinical Trial Registration number: NCT01521312