title: Linagliptin improves endothelial function in patients with type 2 diabetes: A randomized study of linagliptin effectiveness on endothelial function.
abstract: OBJECTIVE
  The present multicenter, prospective, controlled, open and randomized three-arm parallel study was designed to compare the effects of linagliptin with those of metformin on endothelial function.
  
  
  METHODS
  Type 2 diabetes patients treated with 750 mg of metformin (hemoglobin A1c ≥6.0% and <8.0%, n = 96) were randomized to continue metformin 750 mg/day (control group, n = 29), metformin at 1,500 mg/day (metformin group, n = 26) and metformin 750 mg/day supplemented with linagliptin 5 mg/day (linagliptin add-on group, n = 29) and treated for 16 weeks. Vascular endothelial function was evaluated by flow-mediated dilation. The primary end-point was changes in flow-mediated dilation at 16 weeks relative to baseline.
  
  
  RESULTS
  Linagliptin significantly improved flow-mediated dilation from baseline (4.9 ± 2.7%) to 16 weeks (6.3 ± 2.7%, P < 0.05), whereas the other groups did not show any changes. Hemoglobin A1c at 16 weeks was significantly lower in the metformin and linagliptin add-on groups compared with the control (6.6 ± 0.6%, 6.5 ± 0.5% and 7.0 ± 0.6%, respectively). Single and multiple regression analyses showed that apolipoprotein B correlated significantly with change in flow-mediated dilation, and apolipoprotein B was decreased only in the linagliptin add-on group (-6.0 ± 11.3 mg/dL, P < 0.01).
  
  
  CONCLUSIONS
  Linagliptin for 16 weeks improved endothelial function with a modest improvement in glycemic control. This effect was mediated, at least in part, by reduction in apolipoprotein B. Linagliptin has a protective role on endothelial function in patients with type 2 diabetes with moderate hyperglycemia.
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Fumika
authors.initials: F
authors.lastname: Shigiyama
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kumashiro
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Iga
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Nephrology, Tokyo Kyosai Hospital, Tokyo, Japan.|Life Science and Bioethics Research Center, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Kanda
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchino
authors.affiliation: Division of Diabetes, Metabolism and Endocrinology, Department of Medicine, Toho University School of Medicine, Tokyo, Japan.
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000188:drug therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069476:Linagliptin / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D007004:Hypoglycemic Agents; D000069476:Linagliptin; D008687:Metformin
keywords: Endothelial function; Linagliptin; Type 2 diabetes