title: Addition of rosiglitazone to metformin is most effective in obese, insulin-resistant patients with type 2 diabetes.
abstract: OBJECTIVE
  These analyses were undertaken to evaluate the efficacy of the insulin sensitizer rosiglitazone (RSG) when added to the therapy of obese type 2 diabetes mellitus patients (T2DM) taking near-maximal doses (2.5 g/day) of metformin (MET). In obese, insulin-resistant patients with T2DM who are inadequately controlled on MET, the addition of an agent that reduces insulin resistance may be a more rational and innovative approach than the addition of an insulin secretagogue.
  
  
  METHODS
  Data were pooled from two double-blind studies of RSG added to 2.5 g/day MET, involving a total of 550 T2DM patients. Patients were categorized as non-overweight, overweight and obese according to their baseline BMI using WHO criteria (<25 kgm(-2), 25-30 kgm(-2), >30 kgm(-2) respectively).
  
  
  RESULTS
  RSG improved glycaemia (HbA1c) and fasting plasma glucose (FPG) to a clinically significant extent in all three subgroups but the effect was most pronounced in the obese patients. Improvements in HOMA estimates of insulin resistance and beta-cell function were also greatest in the obese patients (4 mg: -16% and +19%; 8 mg: -37% and + 33% respectively), as were reductions in fasting insulin. The profile of adverse events was not demonstrably different in obese patients from the non-obese.
  
  
  CONCLUSIONS
  In obese type 2 diabetic patients inadequately controlled on MET alone, addition of rosiglitazone improves glycaemic control, insulin sensitivity and beta-cell function to a clinically important extent.
authors.affiliation: GlaxoSmithKline, Harlow, UK.
authors.forename: T A
authors.initials: TA
authors.lastname: Jones
authors.forename: M
authors.initials: M
authors.lastname: Sautter
authors.forename: L F
authors.initials: LF
authors.lastname: Van Gaal
authors.forename: N P
authors.initials: NP
authors.lastname: Jones
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001786:Blood Glucose / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance; D007515:Islets of Langerhans / Q000503:physiopathology; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D009765:Obesity; D016032:Randomized Controlled Trials as Topic; D000077154:Rosiglitazone; D013844:Thiazoles / Q000627:therapeutic use*; D045162:Thiazolidinediones
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077154:Rosiglitazone; D013844:Thiazoles; D045162:Thiazolidinediones