Comparison of effects of sitagliptin and voglibose on left ventricular diastolic dysfunction in patients with type 2 diabetes: results of the 3D trial

Abstract

BackgroundLeft ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes.MethodsWe conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e’ velocity and E/e’ ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers.ResultsThe study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e’ velocity and E/e’ ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e’ and E/e’ ratio. Among patients not using pioglitazone, e’ increased and the E/e’ ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (−0.7 ± 0.6 % vs. −0.3 ± 0.4, p < 0.005; −1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups.ConclusionsOur trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes.Trial registrationRegistered at http://www.umin.ac.jp under UMIN000003784

Levosimendan Improves Oxidative Balance in Cardiogenic Shock/Low Cardiac Output Patients

“…It is noteworthy that cardiac oxidative stress has been associated with diastolic dysfunction, as well [41], via changes in Ca 2+ handling. Hence, increased ROS production can impair the activity of Ca 2+ /calmodulin kinase (CaMK) II or SERCA2, or affect Ca 2+ sensitivity of myofilaments.…”

Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors

“…In summary, it remains unclear whether DPP4i cause heart failure and, to add to the uncertainty, results from animal studies show improvement in left ventricular relaxation with the use of DPP4i. Moreover, a human trial using 3D echocardiography reported neutral results in diabetic patients with diastolic dysfunction treated with sitaglipitin . A possible reason for this finding could be that there is no benefit, or that it requires longer treatment in humans to determine either harm or benefit.…”

“…Moreover, a human trial using 3D echocardiography reported neutral results in diabetic patients with diastolic dysfunction treated with sitaglipitin. 72 A possible reason for this finding could be that there is no benefit, or that it requires longer treatment in humans to determine either harm or benefit. DPP4 inhibition may have a role in the progression of atherogenesis, as suggested by recent animal research.…”

Cardiometabolic Syndrome and Increased Risk of Heart Failure

“…Sitagliptin was shown to potentially improve DD [95]. In a large retrospective study, the use of DPP-4 inhibitors compared with sulphonylureas was associated with a reduced risk of hospitalization for HF whereas an earlier comparison of saxagliptin with placebo had demonstrated an increased risk for HF hospitalization [96].…”