ACute and Chronic Effects of Saxagliptin (ACCES)

A Randomized, Double Blind, Placebo Controlled, Pilot Study to Evaluate ACute and Chronic Effects of Saxagliptin on Impaired Glucose Tolerance and micro-and Macro-vascular Integrators

Glucose ACCES study will explore the acute and long term (12-week treatment) effects of saxagliptin in patients with impaired glucose tolerance during fasting and after a standardised breakfast. The investigations will be performed on: glycemic parameters on cardiovascular parameters

The aim of this pilot study is to compare in patients with impaired glucose tolerance the effects of saxagliptin versus placebo: (i) on glucose metabolism (ii) on vago-sympathetic activity, arterial stiffness and endothelial function. A total of 36 patients will be recruited in the department of Endocrinology-Diabetology-Nutrition of Jean VERDIER hospital, AP-HP, Bondy, France. The measurements will be performed in the morning 1) at the time of randomisation (Acute ACCES study) and 2) 11-14 weeks after the beginning of saxagliptin or placebo (Chronic ACCES study). We will evaluate at fasting and each hour after a standardized breakfast: (i) biological and metabolic parameters. Furthermore, an oral glucose tolerance test will be performed at the end of the study. (ii) by non-invasive devices arterial stiffness (Sphygmocor®), endothelial function (ENDOPAT 2000® ), cutaneous microcirculation (laser doppler Perimed ®.PF 5010) and cardiac autonomic function(task force monitor®).

Impaired glucose tolerance, Saxagliptin, Cardiovascular risk integrators, Vago-sympathetic activity, Arterial stiffness, Endothelial function

This is a pilot study. The vascular measurements will be performed before and during a standardized breakfast.

This is a pilot study. The vascular measurements will be performed before and during a standardized breakfast.

This is a pilot study. The vascular measurements will be performed before and during a standardized breakfast.

This is a pilot study. The vascular measurements will be performed before and during a standardized breakfast.

Inclusion Criteria: Social security affiliation Persons without TUTORSHIP that can freely agree to participate to the study Age between 18 to 70 years Impaired glucose tolerance diagnosed during the previous month. Exclusion criteria: Pregnancy Breast feeding Diabetes No contraception Body Mass Index > 45 kg/m² Arterial blood pressure > 160/110 mmHg Creatinine clearance < 60 ml/min Severe hepatocellular insufficiency Chronic respiratory disease Anaemia (Hemoglobin < 10 g/dl) Peripheral arterial occlusive disease Heart failure Cardiac arrhythmia

Rezki A, Cosson E, Fysekidis M, Chiheb S, Vicaut E, Valensi P. 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. Nutr Metab Cardiovasc Dis. 2021 Sep 22;31(10):2945-2958. doi: 10.1016/j.numecd.2021.06.017. Epub 2021 Jul 1.

Rezki A, Fysekidis M, Chiheb S, Vicaut E, Cosson E, Valensi P. Acute and long-term effects of saxagliptin on post-prandial glycemic response in obese patients with impaired glucose tolerance. Nutr Metab Cardiovasc Dis. 2021 Apr 9;31(4):1257-1266. doi: 10.1016/j.numecd.2020.12.025. Epub 2020 Dec 31.