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

Kazufumi Nakamura1*, Hiroki Oe1, Hajime Kihara2, Kenei Shimada3, Shota Fukuda4, Kyoko Watanabe5, Tsutomu Takagi6, Kei Yunoki1, Toru Miyoshi1, Kumiko Hirata7, Junichi Yoshikawa8 and Hiroshi Ito1*

Author Affiliations

1 Department of Cardiovascular Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Okayama 700-8558, Japan

2 Department of Internal Medicine, Kihara Cardiovascular Clinic, Asahikawa, Japan

3 Department of Internal Medicine and Cardiology, Osaka City University of Medicine, Osaka, Japan

4 Department of Medicine, Osaka Ekisaikai Hospital, Osaka, Japan

5 Department of Internal Medicine, Okayama Saiseikai General Hospital, Okayama, Japan

6 Takagi Cardiology Clinic, Kyoto, Japan

7 Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan

8 Nishinomiya Watanabe Cardiovascular Center, Nishinomiya, Japan

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Cardiovascular Diabetology 2014, 13:110  doi:10.1186/s12933-014-0110-2

Published: 30 July 2014



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. 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.


We 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.


ΔFMD 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).


Sitagliptin 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 registration

registered at webcite under UMIN000003951

Dipeptidyl peptidase 4 (DPP-4) inhibitors; Alpha glucosidase inhibitor; Endothelial function; Flow-mediated dilatation; CD34