Abstract
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).
Highlights
Diabetes mellitus is associated with microvascular complications such as diabetic retinopathy and nephropathy [1,2]
The study protocol was approved by the Ethic Committee of the University of ErlangenNuremberg and the study was performed according to Declaration of Helsinki and “good clinical practice” (GCP) guidelines
Female subjects of child bearing potential or within two years of the menopause were excluded unless a pregnancy test at the screening visit was negative and adequate contraceptive precautions made during the study
Summary
Diabetes mellitus is associated with microvascular complications such as diabetic retinopathy and nephropathy [1,2]. Vascular and hemodynamic changes, occurring prior to any clinical manifestation, are hyperperfusion of the retinal and renal circulation, vascular remodeling and an increase in pulse wave reflection leading to an increased aortic pressure [3,4,5]. Saxagliptin is a potent, selective, reversible, and competitive dipeptidyl peptidase-4 (DPP-4) inhibitor [15,16]. Patients with diabetes mellitus are at increased risk for microvascular complications. 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
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