DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study

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

Cardiometabolic Effects of a New Class of Antidiabetic Agents

“…24 In comparison, a Japanese group found a significant improvement in flow-mediated vasodilation in patients treated with sitagliptin due to an increase in CD34 that is a marker of endothelial progenitor cells. 25 Hence, there is a lack of real clarity regarding the effects of DPP-4 inhibitors on endothelial function.…”

Vascular failure and recent anti-diabetic drugs

“…Two papers reported that sitagliptin and trelagliptin did not improve FMD or RH-PAT responses in patients with T2DM when given for three months 61,62) . However, sitagliptin, alogliptin, vildagliptin, and tenegliptin improved endothelial dysfunction in most studies [63][64][65][66][67] . We reported that long-term therapy with sitagliptin failed to improve FMD relative to conventional treatment 61) .…”

“…Adding sitagliptin to conventional antihyperglycemic drugs for two years in patients with T2DM did not alter endothelial function measured by FMD. Antihyperglycemic agents including metformin, pioglitazone, and an α-glucosidase inhibitor have been found to improve glycemic control in patients with T2DM 61,66,[68][69][70] . Based on lowering glucose levels with anti-diabetic drugs, reduction of hyperglycemia may improve endothelial dysfunction clinically.…”

Effects of sitagliptin on coronary atherosclerosis evaluated using integrated backscatter intravascular ultrasound in patients with type 2 diabetes: rationale and design of the TRUST study

“…Indeed, DPP-4 inhibitors have been shown to have anti-inflammatory and anti-atherogenic effects in an animal model [18][19][20]. In addition, DPP-4 inhibitors improve endothelial function [21,22], as well as attenuate neointima formation after vascular injury [23]. It has been speculated that lowering plasma glucose levels using DPP-4 inhibitors or GLP-1 receptor agonists could attenuate the progression of coronary atherosclerosis and lead to a better cardiovascular prognosis.…”