Effects of dipeptidyl peptidase-4 inhibitors on cardiac and endothelial function in type 2 diabetes mellitus: A pilot study

Recent studies have raised concerns regarding increased heart failure in patients on dipeptidyl peptidase-4 inhibitors. We examined whether dipeptidyl peptidase-4 inhibitors, compared to non-incretin-based therapies, have differential effects on left ventricular and endothelial function in patients with type 2 diabetes mellitus.

A total of 25 type 2 diabetes mellitus patients commenced on a dipeptidyl peptidase-4 inhibitor were compared with 50 matched controls. Left ventricular systolic and diastolic function and flow-mediated dilatation were compared before and 12 months after treatment.

At baseline, both dipeptidyl peptidase-4 inhibitor and control groups had elevated HbA1c and comparable subclinical left ventricular dysfunction (left ventricular global longitudinal strain: -15.4% vs -15.9%, p = 0.538; e' velocities: 6 vs 6 cm/s, p = 0.151, where e' is the peak mitral annular early diastolic tissue velocity). After 12 months, both groups had similar improvement in HbA1c. However, patients on dipeptidyl peptidase-4 inhibitors had greater improvement in systolic (ΔGLS: 3.6% vs 1.3%, p < 0.001), despite no significant differences in weight, blood pressure or lipid parameters in both groups. Diastolic (Δe': 38% vs 17%, p = 0.001) and endothelial function improved in the dipeptidyl peptidase-4 inhibitor group but not the control group (ΔFMD: 5% vs -1%, p = 0.029).

We demonstrated significant improvements in LV systolic, diastolic and endothelial function in patients treated with a dipeptidyl peptidase-4 inhibitor over 12 months. These beneficial effects may provide some reassurance regarding the cardiovascular safety of dipeptidyl peptidase-4 inhibitors.