title: Addition of liraglutide in patients with Type 2 diabetes well controlled on metformin monotherapy improves several markers of vascular function.
abstract: OBJECTIVE
  The aim of this study was to investigate the vascular effects of liraglutide in patients well controlled on metformin monotherapy.
  
  
  METHODS
  Forty-four patients with Type 2 diabetes were included in the study. Main inclusion criteria were: pretreatment with metformin on a stable dosage, HbA(1c) < 53 mmol/mol (7.0%), age 30-65 years. Patients were randomized to receive additional liraglutide or to remain on metformin monotherapy. After 6 weeks (1.2 mg) and after 12 weeks (1.8 mg), venous blood was taken for the measurement of several laboratory markers characterizing vascular and endothelial function. In addition, retinal microvascular endothelial function and arterial stiffness were measured.
  
  
  RESULTS
  HbA(1c) levels declined from 45 ± 4 mmol/mol (6.3 ± 0.4%; mean ± SD) to 40 ± 3 mmol/mol (5.8 ± 0.3%) during liraglutide treatment. Asymmetric dimethylarginin was reduced by liraglutide treatment from 0.39 ± 0.08 to 0.35 ± 0.06 μmol/l, E-selectin from 43.6 ± 15.4 to 40.8 ± 15.1 ng/ml, plasminogen activator inhibitor 1 from 861.6 ± 584.3 to 666.1 ± 499.4 ng/ml and intact proinsulin from 9.0 ± 7.2 to 7.0 ± 4.8 pmol/l at 12 weeks of treatment. The microvascular response to flicker light increased from 7.0 ± 15.1 to 15.4 ± 11.5% after 6 weeks and to 11.1 ± 9.9% after 12 weeks. No change could be observed for high-sensitivity C-reactive protein, monocyte chemotactic protein 1, vascular cell adhesion molecule or arterial stiffness parameters.
  
  
  CONCLUSIONS
  In patients with Type 2 diabetes, well controlled with metformin monotherapy, addition of liraglutide improves several cardiovascular risk markers beyond glycaemic control.
authors.affiliation: Institute for Clinical Research and Development, Medical Department, Mainz, Germany. thomasf@ikfe.de
authors.forename: T
authors.initials: T
authors.lastname: Forst
authors.forename: G
authors.initials: G
authors.lastname: Michelson
authors.forename: F
authors.initials: F
authors.lastname: Ratter
authors.forename: M M
authors.initials: MM
authors.lastname: Weber
authors.forename: S
authors.initials: S
authors.lastname: Anders
authors.forename: M
authors.initials: M
authors.lastname: Mitry
authors.forename: B
authors.initials: B
authors.lastname: Wilhelm
authors.forename: A
authors.initials: A
authors.lastname: Pfützner
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D019040:E-Selectin / Q000097:blood*; D004730:Endothelium, Vascular / Q000503:physiopathology; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D000069450:Liraglutide; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011384:Proinsulin / Q000097:blood*; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019040:E-Selectin; D007004:Hypoglycemic Agents; D017395:Plasminogen Activator Inhibitor 1; C018524:N,N-dimethylarginine; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1; D011384:Proinsulin; D008687:Metformin; D001120:Arginine