title: DPP-4 inhibitor and alpha-glucosidase inhibitor equally improve endothelial function in patients with type 2 diabetes: EDGE study.
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.
  
  
  BACKGROUND
  registered at http://www.umin.ac.jp/ctrj/ under UMIN000003951.
authors: Kazufumi
authors: K
authors: Nakamura
authors: Hiroki
authors: H
authors: Oe
authors: Hajime
authors: H
authors: Kihara
authors: Kenei
authors: K
authors: Shimada
authors: Shota
authors: S
authors: Fukuda
authors: Kyoko
authors: K
authors: Watanabe
authors: Tsutomu
authors: T
authors: Takagi
authors: Kei
authors: K
authors: Yunoki
authors: Toru
authors: T
authors: Miyoshi
authors: Kumiko
authors: K
authors: Hirata
authors: Junichi
authors: J
authors: Yoshikawa
authors: Hiroshi
authors: H
authors: Ito
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D005260:Female; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use; D000068900:Sitagliptin Phosphate; D014230:Triazoles / Q000494:pharmacology / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D011719:Pyrazines; D014230:Triazoles; D007294:Inositol; C102817:voglibose; D000068900:Sitagliptin Phosphate