ACute and Chronic Effects of Saxagliptin

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®).

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