title: Pioglitazone and cardiovascular outcomes in patients with insulin resistance, pre-diabetes and type 2 diabetes: a systematic review and meta-analysis.
abstract: To evaluate the effect of pioglitazone in people with insulin resistance, pre-diabetes and type 2 diabetes.
  
  
  
  Systematic review and meta-analysis of randomised, controlled trials.
  
  
  
  Literature searches were performed across PubMed, EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials from 1966 to May 2016 to identify randomised, controlled trials with more than 1 year follow-up.
  
  
  
  Relative risk (RR) with 95% CI was used to evaluate the association between pioglitazone and the risk of major adverse cardiovascular events (MACE: composite of non-fatal myocardial infarction, non-fatal stroke and cardiovascular death) and safety outcomes, after pooling data across trials in a fixed-effects model.
  
  
  
  Nine trials with 12 026 participants were enrolled in the current meta-analysis. Pioglitazone therapy was associated with a lower risk of MACE in patients with pre-diabetes or insulin resistance (RR 0.77, 95% CI 0.64 to 0.93), and diabetes (RR 0.83, 95% CI 0.72 to 0.97). Risks of heart failure (RR 1.32; CI 1.14 to 1.54), bone fracture (RR 1.52, 95% CI 1.17 to 1.99), oedema (RR, 1.63; CI 1.52 to 1.75) and weight gain (RR 1.60; CI 1.50 to 1.72) increased in pioglitazone group.
  
  
  
  Pioglitazone was associated with reduced risk of MACE in people with insulin resistance, pre-diabetes and diabetes mellitus. However, the risks of heart failure, bone fracture, oedema and weight gain were increased.
authors.affiliation: Jia-Yi Clinic, Taoyuan, Taiwan.
authors.forename: Hung-Wei
authors.initials: HW
authors.lastname: Liao
authors.affiliation: UCLA Stroke Center, Los Angeles, California, USA.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Saver
authors.affiliation: Department of Neurology, Research Services Center for Health Information, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Wu
authors.affiliation: Department of Nephrology, School of Medicine, College of Medicine, Taipei Medical University, Wan Fang Hospital, Taipei, Taiwan.
authors.forename: Tso-Hsiao
authors.initials: TH
authors.lastname: Chen
authors.affiliation: Department of Neurology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan.
authors.forename: Meng
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Neurology, Medical University of South Carolina, Charleston, South Carolina, USA.
authors.forename: Bruce
authors.initials: B
authors.lastname: Ovbiagele
mesh_terms: D002318:Cardiovascular Diseases / Q000453:epidemiology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology; D004487:Edema / Q000453:epidemiology; D050723:Fractures, Bone / Q000453:epidemiology; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007333:Insulin Resistance; D000077205:Pioglitazone; D011236:Prediabetic State / Q000188:drug therapy*; D065840:Protective Factors; D016032:Randomized Controlled Trials as Topic; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D015430:Weight Gain
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone