title: A randomized controlled trial examining combinations of repaglinide, metformin and NPH insulin.
abstract: OBJECTIVE
  To compare combination use of repaglinide, metformin and bedtime Neutral Protamine Hagedorn (NPH) insulin with conventional approaches of insulin initiation in patients with Type 2 diabetes (T2DM).
  
  
  METHODS
  Eighty-two patients with T2DM with suboptimal glycaemic control on oral glucose-lowering agents were randomized to one of three treatment regimens for 4 months. Group 1 received metformin and twice daily biphasic 30/70 human insulin mixture (n = 27), group 2 metformin and bedtime NPH insulin (n = 26) and group 3 metformin, bedtime NPH insulin and mealtime repaglinide (n = 25).
  
  
  RESULTS
  Seventy-five patients completed the study. Baseline and end-point mean HbA1c levels fell from 9.0 +/- 1.1 to 7.9 +/- 1.1% in group 1, 10.0 +/- 2.2 to 9.2 +/- 1.4% group 2 and 10.0 +/- 1.7 to 8.1 +/- 1.5% in group 3, respectively. All groups showed improvements in HbA1c. There was no significant difference between groups in the proportions of patients experiencing hypoglycaemia (29.6, 25.0 and 16.7%, respectively; P = 0.55) or in mean weight gain (2.9, 0.7 and 2.2 kg, respectively; P = 0.06). By 4 months, insulin doses were 0.63 +/- 0.32 IU/kg in group 1, 0.58 +/- 0.21 IU/kg in group 2 and 0.37 +/- 0.22 IU/kg in group 3 (group 3 vs. groups 1 and 2: P < 0.002).
  
  
  CONCLUSIONS
  The approach using repaglinide, metformin and NPH insulin improved glycaemic control with a similar safety profile to conventional insulin initiation in T2DM and produced final glycaemic control similar to metformin and a twice daily biphasic insulin mixture.
authors.affiliation: University Hospitals of Leicester NHS Trust, Leicester, UK. melanie.davies@uhl-tr.nhs.uk
authors.forename: M J
authors.initials: MJ
authors.lastname: Davies
authors.forename: P K
authors.initials: PK
authors.lastname: Thaware
authors.forename: J R
authors.initials: JR
authors.lastname: Tringham
authors.forename: J
authors.initials: J
authors.lastname: Howe
authors.forename: J
authors.initials: J
authors.lastname: Jarvis
authors.forename: V
authors.initials: V
authors.lastname: Johnston
authors.forename: D L
authors.initials: DL
authors.lastname: Kitchener
authors.forename: T C
authors.initials: TC
authors.lastname: Skinner
authors.forename: P G
authors.initials: PG
authors.lastname: McNally
authors.forename: I G
authors.initials: IG
authors.lastname: Lawrence
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002219:Carbamates / Q000008:administration & dosage*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007336:Insulin, Isophane / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage*; D016896:Treatment Outcome; D015430:Weight Gain / Q000502:physiology
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; D007336:Insulin, Isophane; C072379:repaglinide; D008687:Metformin