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

Cardiovascular Diabetology

Original Investigation

Iris Kistner¹  Christian Ott¹  Ulrike Raff¹  Stefanie Friedrich¹  Roland E Schmieder¹  Stephanie Schmidt¹  Joanna M Harazny²  Peter Bramlage³ 

[1] Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Ulmenweg 18, Erlangen, Germany;Department of Nephrology and Hypertension, University of Erlangen-Nuremberg, Ulmenweg 18, Erlangen, Germany;Department of Pathophysiology, Warmia Masury University, Olsztyn, Poland;Institut für Pharmakologie und präventive Medizin, Mahlow, Germany;

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

DOI  :  10.1186/1475-2840-13-19

 received in 2013-10-07, accepted in 2014-01-11,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundPatients 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.MethodsIn 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.ResultsPostprandial 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).ConclusionsOur data suggest that treatment with saxagliptin for 6 weeks normalizes retinal capillary flow and improves central hemodynamics in type-2 diabetes.Trial registrationThe study was registered at (ID: NCT01319357).

【 授权许可】

Unknown   
© Ott et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.