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

Amel Rezki (1, 2) , Emmanuel Cosson (1, 2) , Marinos Fysekidis (1, 2) , Sabrina Chiheb (1) , Eric Vicaut (3) , Paul Valensi (1)

1 Service d'endocrinologie diabétologie, nutrition (Hôpital Jean Verdier)
2 UREN - Unité de Recherche en Epidémiologie Nutritionnelle
3 Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]

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/m2) 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.

Keywords: Impaired glucosetolerance; Arterial stiffness; Autonomic nervoussystem; Dipeptidyl peptidaseinhibitor; Endothelium; Microcirculation; Post-prandial; Saxagliptin

Domains: Life Sciences [q-bio]

Amel Rezki, Emmanuel Cosson, Marinos Fysekidis, Sabrina Chiheb, Eric Vicaut, et al.. 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. Nutrition, Metabolism and Cardiovascular Diseases, 2021, 31 (10), pp.2945-2958. ⟨10.1016/j.numecd.2021.06.017⟩. ⟨hal-03500288⟩