title: Effects of linagliptin on renal endothelial function in patients with type 2 diabetes: a randomised clinical trial.
abstract: Endothelial dysfunction predicts cardiovascular damage and renal involvement. Animal experiments and human studies indicate an increased nitric oxide (NO) activity and endothelial NO synthase (NOS) expression in the early stage of type 2 diabetes. The aim of the study was to assess the effect of linagliptin on the endothelial function of the renal vasculature.
  
  
  
  In this randomised, double-blind, parallel-group, investigator-initiated trial, 62 patients with type 2 diabetes were randomly assigned (by computer-generated random code) to receive linagliptin 5 mg (n = 30) or placebo (n = 32) for 4 weeks. The primary objective was to assess endothelial function of the renal vasculature, by constant-infusion input-clearance and urinary albumin/creatinine ratio (UACR), both before and after blockade of NOS with NG-monomethyl-L-arginine (L-NMMA).
  
  
  
  Treatment with linagliptin for 4 weeks reduced fasting, postprandial blood glucose and HbA1c, although not significantly; no change occurred with placebo. Renal plasma flow (RPF) did not change after linagliptin or placebo. After 4 weeks the absolute change in RPF due to L-NMMA was smaller in the linagliptin group than in the placebo group (-46.8 ± 34 vs -65.1 ± 36 ml/min, p = 0.045), indicating a lower basal NO activity after treatment with linagliptin. Consistently, the response of UACR to L-NMMA increased in the placebo group (p = 0.059) but not in the linagliptin group (p = 0.276), pointing to an upregulation of NO activity in the placebo group. No clinically meaningful safety concerns were evident.
  
  
  
  Our data suggest that treatment with the dipeptidyl peptidase-4 inhibitor linagliptin for 4 weeks prevented the impairment of renal endothelial function due to hyperglycaemia in type 2 diabetes.
  
  
  
  ClinicalTrials.gov NCT01835678 FUNDING: : This study was funded by Boehringer Ingelheim.
authors: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), University Hospital, Ulmenweg 18, 91054, Erlangen, Germany.
authors: Christian
authors: C
authors: Ott
authors: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), University Hospital, Ulmenweg 18, 91054, Erlangen, Germany.
authors: Iris
authors: I
authors: Kistner
authors: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), University Hospital, Ulmenweg 18, 91054, Erlangen, Germany.
authors: Mirjam
authors: M
authors: Keller
authors: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), University Hospital, Ulmenweg 18, 91054, Erlangen, Germany.
authors: Stefanie
authors: S
authors: Friedrich
authors: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), University Hospital, Ulmenweg 18, 91054, Erlangen, Germany.
authors: Carsten
authors: C
authors: Willam
authors: Institute for Pharmacology and Preventive Medicine, Mahlow, Germany.
authors: Peter
authors: P
authors: Bramlage
authors: Department of Nephrology and Hypertension, Friedrich-Alexander-University Erlangen-Nürnberg (FAU), University Hospital, Ulmenweg 18, 91054, Erlangen, Germany. roland.schmieder@uk-erlangen.de.
authors: Roland E
authors: RE
authors: Schmieder
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000652:urine; D001786:Blood Glucose / Q000187:drug effects; D003404:Creatinine / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000652:urine*; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000188:drug therapy / Q000652:urine; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D000069476:Linagliptin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D003404:Creatinine; D006442:Glycated Hemoglobin; D000069476:Linagliptin
keywords: DPP-4 inhibitor; Endothelial function; Nitric oxide; Renal; Type 2 diabetes