title: Effect of linagliptin on pulse wave velocity in early type 2 diabetes: A randomized, double-blind, controlled 26-week trial (RELEASE).
abstract: To evaluate the effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin on aortic pulse wave velocity (PWV) as a surrogate marker of arterial stiffness and early atherosclerosis in people with early type 2 diabetes.
  
  
  
  A total of 45 people with type 2 diabetes (median [interquartile range] age 63 [54-66] years, 61% men, mean ± standard deviation glycated haemoglobin [HbA1c] 6.3% ± 0.4% [45 ± 4.6 mmol/mol]), without cardiovascular disease and naïve to antidiabetic treatment, were randomized (1:1) to treatment with linagliptin 5 mg once daily or placebo for 26 weeks in a double-blind fashion. PWV was assessed at baseline, 4 and 26 weeks of treatment, and again at 30, 4 weeks after treatment. The primary endpoint was between-group difference in PWV (corrected for systolic blood pressure [SBP]) at week 26. Secondary endpoints included differences in central SBP and augmentation index (AIx).
  
  
  
  Compared with placebo, 26 weeks of linagliptin decreased PWV by an average of 0.91 m/s (95% confidence interval -1.76 to -0.06; P = .035). PWV returned to baseline after 4 weeks washout. Differences in central SBP and AIx were not different between linagliptin and placebo. Linagliptin decreased HbA1c (-0.4%; P < .001), fasting plasma glucose (-0.7 mmol/L; P = .002) and triglycerides (-0.49 mmol/L; P = .019) as compared with placebo. The changes in body weight, cholesterol and high-sensitivity C-reactive protein did not differ between groups.
  
  
  
  Linagliptin decreased aortic PWV in people with early-stage type 2 diabetes as compared with placebo after 26 weeks of treatment. These results suggest that linagliptin has a favourable effect on arterial stiffness.
authors.affiliation: Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Stefanie A
authors.identifier: 0000-0002-7532-2536
authors.initials: SA
authors.lastname: de Boer
authors.affiliation: Department of Clinical Pharmacy and Pharmacology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Hiddo J L
authors.identifier: 0000-0002-3126-3730
authors.initials: HJL
authors.lastname: Heerspink
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Juárez Orozco
authors.affiliation: Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Arie M
authors.initials: AM
authors.lastname: van Roon
authors.affiliation: Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Pieter W
authors.initials: PW
authors.lastname: Kamphuisen
authors.affiliation: Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: Smit
authors.affiliation: Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.|Department of Biomedical Photonic Imaging, University of Twente, Enschede, The Netherlands.
authors.forename: Riemer H J A
authors.initials: RHJA
authors.lastname: Slart
authors.affiliation: Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Joop D
authors.initials: JD
authors.lastname: Lefrandt
authors.affiliation: Department of Vascular Medicine, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
authors.forename: Douwe J
authors.initials: DJ
authors.lastname: Mulder
mesh_terms: D001011:Aorta; D050197:Atherosclerosis / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control*; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000503:physiopathology / Q000517:prevention & control*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control*; D006973:Hypertension / Q000150:complications / Q000517:prevention & control; D015228:Hypertriglyceridemia / Q000150:complications / Q000503:physiopathology / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D000069476:Linagliptin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D012720:Severity of Illness Index; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D015415:Biomarkers; D054873:Dipeptidyl-Peptidase IV Inhibitors; D006442:Glycated Hemoglobin; D000069476:Linagliptin; C517652:hemoglobin A1c protein, human
keywords: DPP-4 inhibitor; antidiabetic drug; cardiovascular disease; clinical trial; linagliptin; type 2 diabetes