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

Kazufumi Nakamura, Hiroki Oe, Hajime Kihara, Kenei Shimada, Shota Fukuda, Kyoko Watanabe, Tsutomu Takagi, Kei Yunoki, Toru Miyoshi, Kumiko Hirata, Junichi Yoshikawa, Hiroshi Itoh

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Background: 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.Methods: 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.Results: 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).Conclusions: 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.

Original languageEnglish
Article number110
JournalCardiovascular Diabetology
Volume13
Issue number1
DOIs
Publication statusPublished - Jul 30 2014

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Dipeptidyl-Peptidase IV Inhibitors
Type 2 Diabetes Mellitus
Dilatation
Glucagon-Like Peptide 1
Hyperglycemia
C-Peptide
pioglitazone
Oxidative Stress
Therapeutics
Lipids
Glucose Intolerance
Brachial Artery
Glycoside Hydrolase Inhibitors
Metformin
Nausea
Multicenter Studies
Sitagliptin Phosphate
voglibose
Diarrhea
Fasting

Keywords

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

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes : EDGE study. / Nakamura, Kazufumi; Oe, Hiroki; Kihara, Hajime; Shimada, Kenei; Fukuda, Shota; Watanabe, Kyoko; Takagi, Tsutomu; Yunoki, Kei; Miyoshi, Toru; Hirata, Kumiko; Yoshikawa, Junichi; Itoh, Hiroshi.

In: Cardiovascular Diabetology, Vol. 13, No. 1, 110, 30.07.2014.

Research output: Contribution to journalArticle

Nakamura, Kazufumi ; Oe, Hiroki ; Kihara, Hajime ; Shimada, Kenei ; Fukuda, Shota ; Watanabe, Kyoko ; Takagi, Tsutomu ; Yunoki, Kei ; Miyoshi, Toru ; Hirata, Kumiko ; Yoshikawa, Junichi ; Itoh, Hiroshi. / DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes : EDGE study. In: Cardiovascular Diabetology. 2014 ; Vol. 13, No. 1.
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T1 - DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes

T2 - EDGE study

AU - Nakamura, Kazufumi

AU - Oe, Hiroki

AU - Kihara, Hajime

AU - Shimada, Kenei

AU - Fukuda, Shota

AU - Watanabe, Kyoko

AU - Takagi, Tsutomu

AU - Yunoki, Kei

AU - Miyoshi, Toru

AU - Hirata, Kumiko

AU - Yoshikawa, Junichi

AU - Itoh, Hiroshi

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N2 - Background: 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.Methods: 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.Results: 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).Conclusions: 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.

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KW - Alpha glucosidase inhibitor

KW - CD34

KW - Dipeptidyl peptidase 4 (DPP-4) inhibitors

KW - Endothelial function

KW - Flow-mediated dilatation

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