Effects of the DPP-4 inhibitor saxagliptin on early vascular changes in the retinal and systemic circulation

Abstract

In type-2 diabetes early vascular changes (among others) are hyperperfusion in the retinal circulation (like in the kidney) and increased pulse wave reflection leading to increased aortic pressure. We analyzed whether the DPP4-inhibitor saxagliptin reverses early vascular and haemodynamic changes in type-2 diabetes. In this double-blind randomized controlled clinical cross-over trial 42 patients with type-2 diabetes (age 60.3, 13 were females, BMI 30.6 kg/m2, mean duration of diabetes 4 years, HbA1c 7.0%, blood pressure 132/79 mmHg) were consecutively [PB1] included and randomized to placebo or saxagliptin 5 mg for 6 weeks each. Retinal capillary flow (RCF) was assessed at baseline and after flickerlight exposure (as a vasodilatory test) by scanning laser Doppler flowmetry. Central (aortic) systolic blood pressure (SBP), central pulse pressure (PP), augmentation index and pulse wave velocity were determined with the SphygmoCor device. Following treatment with saxagliptin (as opposed to placebo) saxagliptin effected a better glycemic control, a reduced retinal capillary flow (p=0.033) and, in parallel, reduced central systolic augmentation and pulse pressure (see table). In accordance, Flicker light induced increment of RCF (indicative of vasodilatory capacity of the retinal circulation) was numerically 2-fold greater, although not significant. (Table presented) Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central haemodynamics in type 2 diabetes.