title: Pioglitazone Randomised Italian Study on Metabolic Syndrome (PRISMA): effect of pioglitazone with metformin on HDL-C levels in Type 2 diabetic patients.
abstract: BACKGROUND
  Previous evidence indicates that pioglitazone may improve dyslipidemia in patients with Type 2 diabetes mellitus (T2DM).
  
  
  OBJECTIVE
  The primary objective of this study was to evaluate the effect of either pioglitazone or placebo with metformin on levels of serum HDL cholesterol (HDL-C) in patients with T2DM. A secondary objective evaluated changes in metabolic syndrome (MS)-specific parameters.
  
  
  METHODS
  This multicenter, double-blind, randomized study was performed in patients with T2DM treated with metformin and hemoglobin A1c (HbA1c) levels between 6-8%, central obesity and reduced HDL-C. MS was evaluated from global changes in parameter values and expressed as a single factorial score following multivariate analysis of each parameter. 213 patients (110 in the pioglitazone group and 103 in the placebo group) were available for intention-to-treat analysis.
  
  
  RESULTS
  Pioglitazone-treated patients showed a significant increase in HDL-C compared to placebo group (6.3 mg/dl vs 3.0 mg/dl; p<0.01) in addition to a greater reduction in the extent of MS (-13.2 vs -4.9; p=0.0055). Upon study completion, patients treated with pioglitazone had lower levels of HbA1c (6.41±0.65 vs 6.96±0.74%; p<0.001) and homeostasis model assessment-insulin resistance (HOMA-IR) (2.88±1.95 vs 4.68±3.63; p=0.013) and a reduction of the atherogenic LDL subfraction (pattern B) (-5.7%).
  
  
  CONCLUSIONS
  The beneficial effects observed in pioglitazone-treated patients in the present study, (i.e. the increase in HDL-C and the reduction of insulin resistance and atherogenic LDL subfractions), support findings from the PROactive trial, where pioglitazone showed pleiotropic effects and reduced death, fatal myocardial infarction (MI) and non-fatal MI in T2DM patients with MS. Furthermore, medication used in this study showed good tolerability.
authors.affiliation: Diabetes and Metabolic Disease Unit, Cardiovascular and Metabolic Department, IRCCS Multimedica, Sesto San Giovanni, Milan. Italy. stefano.genovese@multimedica.it.
authors.forename: S
authors.initials: S
authors.lastname: Genovese
authors.forename: A
authors.initials: A
authors.lastname: Passaro
authors.forename: P
authors.initials: P
authors.lastname: Brunetti
authors.forename: M
authors.initials: M
authors.lastname: Comaschi
authors.forename: D
authors.initials: D
authors.lastname: Cucinotta
authors.forename: C G
authors.initials: CG
authors.lastname: Egan
authors.forename: B
authors.initials: B
authors.lastname: Chinea
authors.forename: F
authors.initials: F
authors.lastname: Bravi
authors.forename: C
authors.initials: C
authors.lastname: Di Pietro
mesh_terms: D000328:Adult; D000368:Aged; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006706:Homeostasis; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D008954:Models, Biological; D000077205:Pioglitazone; D010919:Placebos; D045162:Thiazolidinediones / Q000008:administration & dosage*
chemical_list: D008076:Cholesterol, HDL; D004338:Drug Combinations; D006442:Glycated Hemoglobin; D008687:Metformin; D000077205:Pioglitazone; D010919:Placebos; D045162:Thiazolidinediones