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

Abstract

Background: Left 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.

Methods: We 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.

Results: The 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.

Conclusions: Our 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 registration: Registered at http://www.umin.ac.jp under UMIN000003784.

Fig. 1

The study’s workflow. Twenty patients were excluded including 6 who were lost to follow-up, 1 who declined to participate and 13 for protocol violation (not meeting inclusion criteria, 12 patients; LVEF < 50 %, 1; under medical treatment with high-dose sulfonylurea). The follow-up study was completed in 77 (77 %) of the patients; 38 received sitagliptin and 39 voglibose

Fig. 2

Changes in e’ and E/e’ between baseline and 24 weeks later. The e’ velocity and E/e’ ratio were comparable between sitagliptin and voglibose groups at baseline. The e’ velocity and E/e’ ratio showed no changes between baseline and a mean of 24 weeks later in both groups. There was also no significant difference in the magnitude of the changes in e’ velocity and E/e’ ratio between the two groups. e’, mitral annular early diastolic velocity; E/e’, ratio of mitral inflow velocity to e’ velocity; W, weeks

Fig. 3

Changes in HbA1c, FBS, GLP-1 and body weight between baseline and 24 weeks later. The decreases in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group. GLP-1 level increased from baseline to 24 weeks later in the sitagliptin group but not in the voglibose group. FBS, fasting blood sugar; GLP-1, glucagon-like peptide-1; HbA1c, hemoglobin A1c; NGSP, National Glycohemoglobin Standardization Program; W, weeks