title: A Randomized Controlled Trial Comparing the Effects of Sitagliptin and Glimepiride on Endothelial Function and Metabolic Parameters: Sapporo Athero-Incretin Study 1 (SAIS1).
abstract: OBJECTIVE
  The DPP-4 inhibitors are incretin-related drugs that improve hyperglycemia in a glucose-dependent manner and have been reported to exert favorable effects on atherosclerosis. However, it has not been fully elucidated whether DPP-4 inhibitors are able to improve endothelial function in patients with type 2 diabetes. Therefore, we investigated the efficacy of sitagliptin, a DPP-4 inhibitor, on endothelial function and glycemic metabolism compared with that of the sulfonylurea glimepiride.
  
  
  METHODS
  In this multicenter, prospective, randomized parallel-group comparison study, 103 outpatients with type 2 diabetes (aged 59.9 ± 9.9 years with HbA1c levels of 7.5 ± 0.4%) with dietary cure only and/or current metformin treatment were enrolled and randomly assigned to receive sitagliptin or glimepiride therapy once daily for 26 weeks. Flow-mediated dilation (FMD), a comprehensive panel of hemodynamic parameters (Task Force® Monitor), and serum metabolic markers were assessed before and after the treatment.
  
  
  RESULTS
  During the study period, no statistically significant change in %FMD was seen in both groups (sitagliptin, 5.6 to 5.6%; glimepiride, 5.6 to 6.0%). Secretory units of islets in transplantation, TNF-α, adiponectin and biological antioxidant potential significantly improved in the sitagliptin group, and superoxide dismutase also tended to improve in the sitagliptin group, while improvements in HbA1c levels were similar between groups. Cardiac index, blood pressure and most other metabolic parameters were not different.
  
  
  CONCLUSIONS
  Regardless of glycemic improvement, early sitagliptin therapy did not affect endothelial function but may provide favorable effects on beta-cell function and on inflammatory and oxidative stress in patients with type 2 diabetes without advanced atherosclerosis.
  
  
  BACKGROUND
  UMIN Clinical Trials Registry System UMIN 000004955.
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nomoto
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Miyoshi
authors.affiliation: Department of Cardiovascular Medicine, NTT East Japan Sapporo Hospital, Sapporo, Japan.|Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Furumoto
authors.affiliation: Department of Biostatistics, School of Public Health, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.|Interfaculty Initiative in Information Studies, The University of Tokyo, Tokyo, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Oba
authors.affiliation: Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tsutsui
authors.affiliation: Japan Community Healthcare and Organization Hokkaido Hospital, Sapporo, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Inoue
authors.affiliation: Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Atsumi
authors.affiliation: Manda Memorial Hospital, Sapporo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Manda
authors.affiliation: Kurihara Clinic, Sapporo, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kurihara
authors.affiliation: Aoki Clinic, Sapporo, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Aoki
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004727:Endothelium / Q000378:metabolism*; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006439:Hemodynamics; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D000068900:Sitagliptin Phosphate / Q000494:pharmacology / Q000627:therapeutic use*; D013453:Sulfonylurea Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D013482:Superoxide Dismutase / Q000378:metabolism; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D052242:Adiponectin; D000975:Antioxidants; D015415:Biomarkers; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000068900:Sitagliptin Phosphate; D013453:Sulfonylurea Compounds; D013482:Superoxide Dismutase; D014409:Tumor Necrosis Factor-alpha; C057619:glimepiride