title: A double-blind randomized study comparing the effects of continuing or not continuing rosiglitazone + metformin therapy when starting insulin therapy in people with Type 2 diabetes.
abstract: OBJECTIVE
  To compare the efficacy and safety of either continuing or discontinuing rosiglitazone + metformin fixed-dose combination when starting insulin therapy in people with Type 2 diabetes inadequately controlled on oral therapy.
  
  
  METHODS
  In this 24-week double-blind study, 324 individuals with Type 2 diabetes inadequately controlled on maximum dose rosiglitazone + metformin therapy were randomly assigned to twice-daily premix insulin therapy (target pre-breakfast and pre-evening meal glucose < or = 6.5 mmol/l) in addition to either rosiglitazone + metformin (8/2000 mg) or placebo.
  
  
  RESULTS
  Insulin dose at week 24 was significantly lower with rosiglitazone + metformin (33.5 +/- 1.5 U/day, mean +/- se) compared with placebo [59.0 +/- 3.0 U/day; model-adjusted difference -26.6 (95% CI -37.7, -15,5) U/day, P < 0.001]. Despite this, there was greater improvement in glycaemic control [HbA(1c) rosiglitazone + metformin vs. placebo 6.8 +/- 0.1 vs. 7.5 +/- 0.1%; difference -0.7 (-0.8, -0.5)%, P < 0.001] and more individuals achieved glycaemic targets (HbA(1c) < 7.0% 70 vs. 34%, P < 0.001). The proportion of individuals reporting at least one hypoglycaemic event during the last 12 weeks of treatment was similar in the two groups (rosiglitazone + metformin vs. placebo 25 vs. 27%). People receiving rosiglitazone + metformin in addition to insulin reported greater treatment satisfaction than those receiving insulin alone. Both treatment regimens were well tolerated but more participants had oedema [12 (7%) vs. 4 (3%)] and there was more weight gain [3.7 vs. 2.6 kg; difference 1.1 (0.2, 2.1) kg, P = 0.02] with rosiglitazone + metformin.
  
  
  CONCLUSIONS
  Addition of insulin to rosiglitazone + metformin enabled more people to reach glycaemic targets with less insulin, and was generally well tolerated.
authors.affiliation: School of Medical Sciences--Diabetes, The Medical School, Newcastle University, Newcastle upon Tyne, UK. philip.home@newcastle.ac.uk
authors.forename: P D
authors.initials: PD
authors.lastname: Home
authors.forename: C J
authors.initials: CJ
authors.lastname: Bailey
authors.forename: J
authors.initials: J
authors.lastname: Donaldson
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: M W
authors.initials: MW
authors.lastname: Stewart
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004338:Drug Combinations; D004359:Drug Therapy, Combination; D005060:Europe; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D013844:Thiazoles / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D004338:Drug Combinations; D007004:Hypoglycemic Agents; D007328:Insulin; D013844:Thiazoles; C471074:rosiglitazone-metformin combination; D008687:Metformin