title: Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study.
abstract: OBJECTIVE
  Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients.
  
  
  METHODS
  Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed.
  
  
  RESULTS
  Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2)  < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups.
  
  
  CONCLUSIONS
  Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.
authors.affiliation: Diabetes Care Unit, Department of Internal Medicine, Catholic University School of Medicine, Rome, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Pitocco
authors.forename: F
authors.initials: F
authors.lastname: Zaccardi
authors.forename: P
authors.initials: P
authors.lastname: Tarzia
authors.forename: M
authors.initials: M
authors.lastname: Milo
authors.forename: G
authors.initials: G
authors.lastname: Scavone
authors.forename: P
authors.initials: P
authors.lastname: Rizzo
authors.forename: F
authors.initials: F
authors.lastname: Pagliaccia
authors.forename: R
authors.initials: R
authors.lastname: Nerla
authors.forename: A
authors.initials: A
authors.lastname: Di Franco
authors.forename: A
authors.initials: A
authors.lastname: Manto
authors.forename: B
authors.initials: B
authors.lastname: Rocca
authors.forename: G A
authors.initials: GA
authors.lastname: Lanza
authors.forename: F
authors.initials: F
authors.lastname: Crea
authors.forename: G
authors.initials: G
authors.lastname: Ghirlanda
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D001916:Brachial Artery / Q000187:drug effects* / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D015237:Dinoprost / Q000378:metabolism; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D010865:Pilot Projects; D016896:Treatment Outcome; D014664:Vasodilation / Q000187:drug effects
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D015237:Dinoprost; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; C517652:hemoglobin A1c protein, human