title: Impact of metformin versus repaglinide on non-glycaemic cardiovascular risk markers related to inflammation and endothelial dysfunction in non-obese patients with type 2 diabetes.
abstract: OBJECTIVE
  In patients with type 2 diabetes mellitus (T2DM), biomarkers reflecting inflammation and endothelial dysfunction have been linked to cardiovascular disease (CVD biomarkers) and metabolic regulation. In T2DM patients, metformin and insulin secretagogues have demonstrated equal anti-hyperglycaemic potency. Here, we report the effect of metformin versus an insulin secretagogue, repaglinide, on CVD biomarkers in non-obese T2DM patients.
  
  
  METHODS
  Single-centre, double-masked, double-dummy, crossover study during 2x4 months involving 96 non-obese (body mass index< or =27 kg/m(2)) insulin-naïve T2DM patients. At enrolment, previous oral hypoglycaemic agents were stopped and the patients entered a 1-month run-in on diet-only treatment. Hereafter, patients were randomized to either 2 mg repaglinide thrice daily followed by 1 g metformin twice daily or vice versa each during 4 months with a 1-month washout between interventions.
  
  
  RESULTS
  Levels of tumour necrosis factor-alpha, plasminogen activator inhibitor-1 antigen, tissue-type plasminogen activator antigen, von Willebrand factor, soluble intercellular adhesion molecule-1 and soluble E-selectin were significantly lower during metformin versus repaglinide treatments. In contrast, Amadori albumin and heart rate were higher during metformin versus repaglinide. Levels of interleukin-6, fibrinogen, soluble vascular cell adhesion molecule-1, asymmetric dimethylarginine and advanced glycation end products as well as glycaemic levels (previously reported) and 24-h blood pressure were similar between treatments. Adjustment for known macrovascular disease did not affect the between-treatment effects.
  
  
  CONCLUSIONS
  In non-obese T2DM patients, metformin was more effective in reducing selected biomarkers reflecting inflammation and endothelial dysfunction compared with repaglinide despite similar glycaemic levels between treatments.
authors.affiliation: Steno Diabetes Center, Niels Steensens Vej 2, 2820 Gentofte, Denmark. sqrl@steno.dk
authors.forename: Søren S
authors.initials: SS
authors.lastname: Lund
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
authors.forename: Jørgen
authors.initials: J
authors.lastname: Gram
authors.forename: Kaj
authors.initials: K
authors.lastname: Winther
authors.forename: Merete
authors.initials: M
authors.lastname: Frandsen
authors.forename: Ulla M
authors.initials: UM
authors.lastname: Smidt
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Hans-Henrik
authors.initials: HH
authors.lastname: Parving
authors.forename: Allan A
authors.initials: AA
authors.lastname: Vaag
mesh_terms: D000368:Aged; D001786:Blood Glucose; D001835:Body Weight; D002219:Carbamates / Q000008:administration & dosage*; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D003925:Diabetic Angiopathies / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D012307:Risk Factors; D016896:Treatment Outcome; D014657:Vasculitis / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D008687:Metformin