DPP-4 inhibition may reduce vascular stiffness
medwireNews: A randomized trial shows that the dipeptidyl peptidase (DPP)-4 inhibitor linagliptin has a rapid and reversible beneficial effect on arterial stiffness.
The findings support those of previous studies, but the researchers say theirs is the first to be designed specifically for the purpose and to include a placebo-treated group.
The study included 44 patients with newly diagnosed type 2 diabetes, without established cardiovascular (CV) disease, who had not yet received any antidiabetic medication. During 26 weeks of treatment, pulse wave velocity (PWV; a measure of arterial stiffness) fell from 8.7 to 8.3 m/s in patients randomly assigned to take linagliptin 5 mg once daily, whereas it rose from 8.8 to 9.2 m/s in those taking placebo.
The PWV reduction in the linagliptin group was seen at the 4-week check-up, and the overall 0.91 m/s difference in PWV change between the two groups at week 26 was statistically significant.
For comparison, a PWV increase of 1.0 m/s is reportedly associated with a CV risk increase of about 15%, after accounting for age, gender, and other risk factors, say Stefanie de Boer (University Medical Center Groningen, the Netherlands) and study co-authors.
PWV returned to baseline levels in patients in the linagliptin group by 4 weeks after the end of the treatment period.
“This indicates that the decrease in PWV is a fast acting and reversible dynamic effect,” writes the team in Diabetes, Obesity and Metabolism.
The augmentation index did not change in either group during treatment, but the researchers say that this is a less direct measure of arterial stiffness than PWV is, being more influenced by heart rate and blood pressure.
Linagliptin also had no effect on systolic blood pressure, leading de Boer and team to suggest that its effect may be mediated via an effect on the peripheral vasculature, independently of the influence of blood pressure, although they note that the underlying mechanism is not clear.
The researchers observe that clinical trials to date have not demonstrated CV benefits for patients taking DPP-4 inhibitors, but point out that these studies were designed to assess CV safety rather than efficacy. They suggest that two forthcoming trials of DPP-4 inhibitors in patients at high CV risk (CAROLINA and CARMELINA) may throw more light on the subject, and establish if any effects are independent of glucose reductions.
medwireNews is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2017