title: Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial.
abstract: OBJECTIVE
  To study the effect of insulin treatment in combination with metformin or an insulin secretagogue, repaglinide, on glycaemic regulation in non-obese patients with type 2 diabetes.
  
  
  METHODS
  Randomised, double blind, double dummy, parallel trial.
  
  
  METHODS
  Secondary care in Denmark between 2003 and 2006.
  
  
  METHODS
  Non-obese patients (BMI </=27) with preserved beta cell function.
  
  
  METHODS
  After a four month run-in period with repaglinide plus metformin combination therapy, patients with a glycated haemoglobin (HbA(1c)) concentration of 6.5% or more were randomised to repaglinide 6 mg or metformin 2000 mg. All patients also received biphasic insulin aspart 70/30 (30% soluble insulin aspart and 70% intermediate acting insulin aspart) 6 units once a day before dinner for 12 months. Insulin dose was adjusted aiming for a fasting plasma glucose concentration of 4.0-6.0 mmol/l. The target of HbA(1c) concentration was less than 6.5%. Treatment was intensified to two or three insulin injections a day if glycaemic targets were not reached.
  
  
  METHODS
  HbA(1c) concentration.
  
  
  RESULTS
  Of the 459 patients who were eligible, 102 were randomised, and 97 completed the trial. Patients had had type 2 diabetes for approximately 10 years. At the end of treatment, HbA(1c) concentration was reduced by a similar amount in the two treatment groups (insulin plus metformin: mean (standard deviation) HbA(1c) 8.15% (1.32) v 6.72% (0.66); insulin plus repaglinide: 8.07% (1.49) v 6.90% (0.68); P=0.177). Total daily insulin dose and risk of hypoglycaemia were also similar in the two treatment groups. Weight gain was less with metformin plus biphasic insulin aspart 70/30 than with repaglinide plus biphasic insulin aspart 70/30 (difference in mean body weight between treatments -2.51 kg, 95% confidence interval -4.07 to -0.95).
  
  
  CONCLUSIONS
  In non-obese patients with type 2 diabetes and poor glycaemic regulation on oral hypoglycaemic agents, overall glycaemic regulation with insulin in combination with metformin was equivalent to that with insulin plus repaglinide. Weight gain seemed less with insulin plus metformin than with insulin plus repaglinide.
  
  
  BACKGROUND
  NCT00118963.
authors.affiliation: Steno Diabetes Center, 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: Merete
authors.initials: M
authors.lastname: Frandsen
authors.forename: Bente B
authors.initials: BB
authors.lastname: Nielsen
authors.forename: Birgitte V
authors.initials: BV
authors.lastname: Hansen
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: D001786:Blood Glucose / Q000378:metabolism; D002219:Carbamates / Q000008:administration & dosage* / Q000009:adverse effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000009:adverse effects / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D061267:Insulin Aspart; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D010349:Patient Compliance; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D015430:Weight Gain
chemical_list: D001786:Blood Glucose; D002219:Carbamates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D061267:Insulin Aspart; D008687:Metformin; D010880:Piperidines; C072379:repaglinide