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 placebo-controlled study.

Background and Aims: Studies of dipeptidyl peptidase inhibitors (DPP4is) report heterogeneous effects on cardiovascular targets in type 2 diabetes. This study aimed to investigate, in patients with impaired glucose tolerance (IGT), whether saxagliptin, a DPP4i, had beneficial cardiovascular effects at fasting and during the post-prandial state.
Methods and Results: In this randomized, placebo-controlled, double-blind, single-center pilot exploratory study, we included obese individuals with IGT. Twenty-four individuals (BMI 36.8 ± 4.8 kg/m 2 ) were randomized to receive for 12 weeks either saxagliptin 5 mg a day or placebo. They were explored 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®). 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, the effects of saxagliptin on the large set of cardiovascular parameters measured are neutral, except for a more marked post-prandial depression of vagal activity.
Clinical Trial Registration Number: NCT01521312.
Competing Interests: Declaration of competing interest Amel Rezki, Marinos Fysekidis and Sabrina Chiheb declare they do not have any conflict of interest in relation with this manuscript. Eric Vicaut declares counseling activities for Abbott, Boston, Genomichealth, Celgen, CEMKA, Bristol-Myers-Squibb, CreativPharmaceuticals, Genomic health, and having received research grants from Astra-Zeneca, Bristol-Myers-Squibb and Pfizer. Emmanuel Cosson declares counseling activities for Abbott, AlphaDiab, Ascencia, Lilly, Medtronic, Merck-Sharp-Dohme, Novartis, Novo-Nordisk, Roche Diagnostics, Sanofi-Aventis, YpsoMed; having given lectures for Abbott, Astra-Zeneca, Bezins, Bristol-Myers-Squibb, LifeScan, Lilly, Merck-Sereno, Novartis, Novo-Nordisk, Roche Diagnostics, Sanofi-Aventis; and received research grants from Abbott, Air Liquide, Astra-Zeneca, Lilly, Novo-Nordisk, Roche diagnostics, Sanofi-Aventis, Ypsomed. Paul Valensi declares having given lectures for Abbott, AstraZeneca, Bayer, Eli-Lilly, Hikma, Merck-Sharp-Dohme, Novo-Nordisk, Novartis, Pfizer, Sanofi, Servier; received research grants from Abbott, Bristol-Myers-Squibb-AstraZeneca, Novo-Nordisk; and participated to Expert Committees for Astra Zeneca, Boehringer Ingelheim, Merck-Serono, Novo-Nordisk, Daiichi-Sankyo, Sanofi, Servier.
(Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)