title: Comparison of pioglitazone with other antidiabetic drugs for associated incidence of liver failure: no evidence of increased risk of liver failure with pioglitazone.
abstract: OBJECTIVE
  The aim of this study was to assess the incidence of liver failure in association with antidiabetic treatment using pioglitazone vs. other oral antidiabetic medications.
  
  
  METHODS
  The study was a retrospective analysis of claim data from the PharMetrics Patient-Centric Database that had over 1.12 million enrollees with type 2 diabetes. All patients, > or =18 years of age with type 2 diabetes, who had initiated treatment either with a thiazolidinedione (pioglitazone and rosiglitazone), sulfonylurea or metformin were identified and matched on the basis of propensity scores, which served as a proxy for severity of disease. The primary measure of interest was the incidence of liver failure or hepatitis post-index date. In addition to unadjusted comparisons, Cox proportional hazard models were employed to estimate the risk of developing liver failure or hepatitis.
  
  
  RESULTS
  There was no significant difference in the 1- and 2-year incidence rates of liver failure or hepatitis (primary and secondary diagnoses) between the pioglitazone monotherapy group and the respective comparator groups. In Cox proportional hazard models controlling for age, pre-index total healthcare costs, Charlson comorbidity index, procedures and a hospitalization or Emergency room (ER) visit for pre-index hyperglycaemia, and pioglitazone were not associated with an increased risk of liver failure or hepatitis, compared to all other defined groups. Furthermore, no primary or secondary diagnosis of liver failure was reported in the pioglitazone group during the follow-up period.
  
  
  CONCLUSIONS
  Results of retrospective data analysis demonstrate no evidence of increased risk of liver failure or hepatitis for patients initiating therapy on pioglitazone, compared to other oral antidiabetic agents. Pioglitazone therapy was not associated with an increased risk of liver failure at 2 years relative to other oral antidiabetic therapies.
authors.affiliation: Takeda Pharmaceuticals North America, Inc., Lincolnshire, IL 60069, USA. rrajagopalan@takedapharm.com
authors.forename: R
authors.initials: R
authors.lastname: Rajagopalan
authors.forename: S
authors.initials: S
authors.lastname: Iyer
authors.forename: A
authors.initials: A
authors.lastname: Perez
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects*; D017093:Liver Failure / Q000139:chemically induced*; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D000077205:Pioglitazone; D012189:Retrospective Studies; D012307:Risk Factors; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000009:adverse effects; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D000077205:Pioglitazone