title: Effects of biphasic, basal-bolus or basal insulin analogue treatments on carotid intima-media thickness in patients with type 2 diabetes mellitus: the randomised Copenhagen Insulin and Metformin Therapy (CIMT) trial.
abstract: OBJECTIVE
  To assess the effect of 3 insulin analogue regimens on change in carotid intima-media thickness (IMT) in patients with type 2 diabetes.
  
  
  METHODS
  Investigator-initiated, randomised, placebo-controlled trial with a 2 × 3 factorial design, conducted at 8 hospitals in Denmark.
  
  
  METHODS
  Participants with type 2 diabetes (glycated haemoglobin (HbA1c) ≥ 7.5% (≥ 58 mmol/mol), body mass index >25 kg/m(2)) were, in addition to metformin versus placebo, randomised to 18 months open-label biphasic insulin aspart 1-3 times daily (n=137) versus insulin aspart 3 times daily in combination with insulin detemir once daily (n=138) versus insulin detemir alone once daily (n=137), aiming at HbA1c ≤ 7.0% (≤ 53 mmol/mol).
  
  
  RESULTS
  Primary outcome was change in mean carotid IMT (a marker of subclinical cardiovascular disease). HbA1c, insulin dose, weight, and hypoglycaemic and serious adverse events were other prespecified outcomes.
  
  
  RESULTS
  Carotid IMT change did not differ between groups (biphasic -0.009 mm (95% CI -0.022 to 0.004), aspart+detemir 0.000 mm (95% CI -0.013 to 0.013), detemir -0.012 mm (95% CI -0.025 to 0.000)). HbA1c was more reduced with biphasic (-1.0% (95% CI -1.2 to -0.8)) compared with the aspart+detemir (-0.4% (95% CI -0.6 to -0.3)) and detemir (-0.3% (95% CI -0.4 to -0.1)) groups (p<0.001). Weight gain was higher in the biphasic (3.3 kg (95% CI 2.7 to 4.0) and aspart+detemir (3.2 kg (95% CI 2.6 to 3.9)) compared with the detemir group (1.9 kg (95% CI 1.3 to 2.6)). Insulin dose was higher with detemir (1.6 IU/kg/day (95% CI 1.4 to 1.8)) compared with biphasic (1.0 IU/kg/day (95% CI 0.9 to 1.1)) and aspart+detemir (1.1 IU/kg/day (95% CI 1.0 to 1.3)) (p<0.001). Number of participants with severe hypoglycaemia and serious adverse events did not differ.
  
  
  CONCLUSIONS
  Carotid IMT change did not differ between 3 insulin regimens despite differences in HbA1c, weight gain and insulin doses. The trial only reached 46% of planned sample size and lack of power may therefore have affected our results.
  
  
  BACKGROUND
  NCT00657943.
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark Department of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Department of Paediatrics, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Lundby-Christensen
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark University of Copenhagen, Copenhagen, Denmark.
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark Department of Health, University of Aarhus, Aarhus, Denmark.
authors.forename: Lise
authors.initials: L
authors.lastname: Tarnow
authors.affiliation: Department of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Almdal
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark Boehringer Ingelheim Pharma GmbH & Co KG, Ingelheim, Germany.
authors.forename: Søren S
authors.initials: SS
authors.lastname: Lund
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Jørn
authors.initials: J
authors.lastname: Wetterslev
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Christian
authors.initials: C
authors.lastname: Gluud
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Trine W
authors.initials: TW
authors.lastname: Boesgaard
authors.affiliation: Department of Physiology and Nuclear Medicine, Frederiksberg, Copenhagen University Hospital, Frederiksberg, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Wiinberg
authors.affiliation: Department of Endocrinology, Bispebjerg, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Perrild
authors.affiliation: Department of Endocrinology, Bispebjerg, Copenhagen University Hospital, Copenhagen, Denmark.
authors.forename: Thure
authors.initials: T
authors.lastname: Krarup
authors.affiliation: Department of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Ole
authors.initials: O
authors.lastname: Snorgaard
authors.affiliation: Department of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark.
authors.forename: Birthe
authors.initials: B
authors.lastname: Gade-Rasmussen
authors.affiliation: University of Copenhagen, Copenhagen, Denmark Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark.
authors.forename: Birger
authors.initials: B
authors.lastname: Thorsteinsson
authors.affiliation: Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark Department of Medicine, Gentofte, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Røder
authors.affiliation: Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark University of Copenhagen, Copenhagen, Denmark.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Mathiesen
authors.affiliation: Department of Endocrinology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Tonny
authors.initials: T
authors.lastname: Jensen
authors.affiliation: University of Copenhagen, Copenhagen, Denmark Department of Endocrinology, Herlev, Copenhagen University Hospital, Herlev, Denmark Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik
authors.initials: H
authors.lastname: Vestergaard
authors.affiliation: Department of Medicine, University Hospital Køge, Køge, Denmark.
authors.forename: Christoffer
authors.initials: C
authors.lastname: Hedetoft
authors.affiliation: Department of Medicine, University Hospital Køge, Køge, Denmark.
authors.forename: Leif
authors.initials: L
authors.lastname: Breum
authors.affiliation: Department of Medicine, Gentofte, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Elsebeth
authors.initials: E
authors.lastname: Duun
authors.affiliation: Department of Medicine, Gentofte, Copenhagen University Hospital, Gentofte, Denmark.
authors.forename: Simone B
authors.initials: SB
authors.lastname: Sneppen
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark University of Copenhagen, Copenhagen, Denmark Section of Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Copenhagen Trial Unit, Centre for Clinical Intervention Research, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark Department of Cardiology, Nephrology and Endocrinology, Nordsjællands University Hospital-Hillerød, Hillerød, Denmark.
authors.forename: Bianca
authors.initials: B
authors.lastname: Hemmingsen
authors.affiliation: Steno Diabetes Center, Gentofte, Denmark.
authors.forename: Bendix
authors.initials: B
authors.lastname: Carstensen
authors.affiliation: Department of Endocrinology, Hvidovre, Copenhagen University Hospital, Hvidovre, Denmark University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
mesh_terms: D001786:Blood Glucose / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D059168:Carotid Intima-Media Thickness; D003718:Denmark; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use*; D061267:Insulin Aspart / Q000008:administration & dosage / Q000627:therapeutic use; D000069057:Insulin Detemir / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D000069057:Insulin Detemir; D008687:Metformin
keywords: ULTRASONOGRAPHY