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Open Access Highly Accessed Original investigation

Effects of saxagliptin on early microvascular changes in patients with type 2 diabetes

Christian Ott1, Ulrike Raff1, Stephanie Schmidt1, Iris Kistner1, Stefanie Friedrich1, Peter Bramlage2, Joanna M Harazny13 and Roland E Schmieder1*

Author Affiliations

1 Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Ulmenweg 18, Erlangen, Germany

2 Institut für Pharmakologie und präventive Medizin, Mahlow, Germany

3 Department of Pathophysiology, Warmia Masury University, Olsztyn, Poland

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Cardiovascular Diabetology 2014, 13:19  doi:10.1186/1475-2840-13-19

Published: 14 January 2014

Abstract

Background

Patients with diabetes mellitus are at increased risk for microvascular complications. Early changes in microcirculation are characterized by hyperperfusion (e.g. in the retina and kidney) and increased pulse wave reflection leading to increased aortic pressure. We investigated the effects of the DPP-4-inhibitor saxagliptin on early retinal microvascular changes.

Methods

In this double-blind, controlled, cross-over trial 50 patients (without clinical signs of microvascular alterations) with type-2 diabetes (mean duration of 4 years) were randomized to receive placebo or 5 mg saxagliptin for 6 weeks. Retinal arteriolar structure and retinal capillary flow (RCF) at baseline and during flicker-light exposure was assessed by scanning laser Doppler flowmetry. Central hemodynamics were assessed by pulse wave analysis.

Results

Postprandial blood glucose (9.27 ± 0.4 versus 10.1 ± 0.4 mmol/L; p = 0.001) and HbA1c (6.84 ± 0.15 (51 ± 1.6) versus 7.10 ± 0.17% (54 ± 1.9 mmol/mol); p < 0.001) were significantly reduced with saxagliptin treatment compared to placebo. RCF was significantly reduced after treatment with saxagliptin (288 ± 13.2 versus 314 ± 14.1 AU; p = 0.033). This was most pronounced in a subgroup of patients (n = 32) with a fall in postprandial blood glucose (280 ± 12.1 versus 314 ± 16.6 AU; p = 0.011). No significant changes in RCF were seen during flicker-light exposure between placebo and saxagliptin, but the vasodilatory capacity increased two-fold with saxagliptin treatment. Central augmentation pressure tended to be lower after treatment with saxagliptin (p = 0.094), and central systolic blood pressure was significantly reduced (119 ± 2.3 versus 124 ± 2.3 mmHg; p = 0.038).

Conclusions

Our data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central hemodynamics in type-2 diabetes.

Trial registration

The study was registered at (ID: NCT01319357).

Keywords:
Saxagliptin; DPP-4 inhibitor; Type-2 diabetes; Retinal blood flow; Central hemodynamics