Physicians' Academy for Cardiovascular Education

DPP-4 inhibitor decreases aortic pulse wave velocity in diabetic patients

Effect of linagliptin on pulse wave velocity in early type 2 diabetes (RELEASE): a randomized, double-blind, controlled 26-week trial

de Boer SA, Heerspink HJL, Juárez Orozco LE, et al. - Diabetes, Obesity and Metabolism 2017; published online ahead of print


DPP-4 inhibitors effectively reduce glycated hemoglobulin (HbA1c) levels, without inducing hypoglycaemia, and have a neutral effect on weight [1]. They inhibit the DPP-4 enzyme, which splits incretins such as glucagon-like peptide 1 (GLP-1). GLP-1 controls glucose dependent insulin secretion. DPP-4 also splits multiple substrates that influence the cardiovascular (CV) system, like the chemokine stromal cell-derived factor- 1α (SDF-1α) that is responsible for the recruitment of endothelial progenitor cells. This suggests that DPP-4 inhibition may have favourable CV effects on top of glucose lowering [2].

Arterial stiffness can be assessed by means of aortic pulse wave velocity (PWV), central systolic blood pressure (SBP) and augmentation index (AIx). PWV is a strong independent predictor of future CV events and all-cause mortality in the general population [3,4].

In the RELEASE trial, the effects on PWV, central SBP and AIx of 26 weeks treatment with the DPP-4 inhibitor linagliptin were evaluated in 44 individuals with recent type 2 diabetes mellitus (T2DM) diagnosis (so naïve to antidiabetic treatment), who were randomly assigned to receive linagliptin or placebo.

Main results


These data may confirm the hypothesis based on previous observations, that linagliptin exert favourable vascular effects beyond glucose-lowering. Compared with placebo, linagliptin decreased aortic PWV, a measure of arterial stiffness and predictor of CV events, in 44 early T2DM subjects after 26 weeks of treatment. This suggest that linagliptin has a favourable effect on arterial stiffness and further studies need to assess whether this translates to improvement of CV outcome on the long-term.


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