Abstract
BackgroundAlpha glucosidase inhibitor (GI) attenuates postprandial hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes. Dipeptidyl peptidase 4 (DPP-4) inhibitors also attenuate PPH. PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis. Furthermore, DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism. However, the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully elucidated. We compared the effects of sitagliptin, a DPP-4 inhibitor, and voglibose, an alpha GI, on endothelial function in patients with diabetes.MethodsWe conducted a randomized prospective multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea, metformin or pioglitazone treatment; 31 patients received sitagliptin treatment and 35 patients, voglibose treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment. The primary endpoint was a change in FMD (ΔFMD) from the baseline to the end of follow-up. The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD, age, sex, current smoking, diabetes duration and body mass index. Secondary efficacy measures included changes in HbA1c, GIP, GLP-1, C-peptide, CD34, lipid profile, oxidative stress markers, inflammatory markers and eGFR and any adverse events.ResultsΔFMD was significantly improved after 12 weeks of treatment in both groups, and there was no significant difference in ΔFMD between the two groups. There were no significant differences in changes in HbA1c, GIP, GLP-1, C-peptide, lipid profile, oxidative stress marker, inflammatory marker and eGFR between the two groups. Compared with voglibose, sitagliptin significantly increased the circulating CD34, a marker of endothelial progenitor cells. Adverse events were observed in 5 patients in only the voglibose group (diarrhea 1, nausea 1, edema 2 and abdominal fullness 1).ConclusionsSitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes. Sitagliptin had protective effects on endothelial function without adverse events.Trial registrationregistered at http://www.umin.ac.jp/ctrj/ under UMIN000003951
Highlights
Postprandial hyperglycemia (PPH) plays a major role in cardiovascular complications in patients with type 2 diabetes [1] and impaired glucose tolerance (IGT) [2]
The age range was quite wide in our study, but there was no significant difference in age or baseline flow-mediated dilatation (FMD) between the two groups
The primary endpoint Change in FMD (ΔFMD) was significantly improved after 12 weeks of treatment in both groups, and there was no significant difference in ΔFMD between the two groups (Table 2 and Figure 2)
Summary
Postprandial hyperglycemia (PPH) plays a major role in cardiovascular complications in patients with type 2 diabetes [1] and impaired glucose tolerance (IGT) [2]. An alpha GI, improves postprandial endothelial dysfunction in patients with type 2 diabetes [9,10] and reduces the risk of cardiovascular events in patients with type 2 diabetes [11] and IGT [12,13]. Glucagon-like peptide-1 (GLP-1), an incretin, induces an endothelialdependent relaxation via NO-dependent action [15] and improves endothelial dysfunction in patients with type 2 diabetes [16], and sitagliptin, a DPP-4 inhibitor, protects endothelial function in spontaneously hypertensive rats through a GLP-1-dependent mechanism [17]. Alpha glucosidase inhibitor (GI) attenuates postprandial hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes. We compared the effects of sitagliptin, a DPP-4 inhibitor, and voglibose, an alpha GI, on endothelial function in patients with diabetes
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