title: The effect of withdrawal of rosiglitazone on treatment pathways, diabetes control and patient outcomes: a retrospective cohort study.
abstract: OBJECTIVE
  To describe the withdrawal of rosiglitazone and the impact upon glycaemic control; intensification of therapy; and progression to major adverse cardiovascular events (MACE), cancer and mortality.
  
  
  METHODS
  Data were from the Clinical Practice Research Datalink (CPRD), a longitudinal U.K. database. Rosiglitazone use was profiled from launch (2000) until withdrawal (2010). Patients discontinuing from July 2010 were included in the analysis to ascertain the impact on glycaemic control; therapy intensification; and progression to MACE, death and cancer. For comparison, patients were matched to those maintained on pioglitazone as a control group.
  
  
  RESULTS
  Rosiglitazone use peaked in May 2007. Of patients prescribed rosiglitazone at discontinuation 54.1% patients used a dual-therapy regimen; most commonly with metformin (46.7%). 65.1% patients remained at the same stage of the diabetes pathway following discontinuation. 51.7% of patients replaced rosiglitazone with pioglitazone. Patients discontinuing were more likely (HR=2.29), to subsequently intensify therapy than controls. After discontinuation of rosiglitazone there was a significant increase in HbA1c, from a median of 6.9% to 7.3%. In matched analysis, there was a significantly greater increase in HbA1c for rosiglitazone patients (0.33% versus 0.10%). Following discontinuation, crude rates for MACE, cancer and mortality were 8.4, 17.9 and 15.8 pkpy, respectively. None was significantly different in the matched analysis.
  
  
  CONCLUSIONS
  Withdrawal of rosiglitazone was associated with worsening glucose control and subsequent intensification of treatment regimen.
authors: Public Health and Primary Care, School of Medicine, Cardiff University, Cardiff UK.
authors: Christopher Ll
authors: CL
authors: Morgan
authors: Health Economics and Outcomes Research, Takeda Europe, London, UK.
authors: Jorge
authors: J
authors: Puelles
authors: Public Health and Primary Care, School of Medicine, Cardiff University, Cardiff UK.
authors: Chris D
authors: CD
authors: Poole
authors: Public Health and Primary Care, School of Medicine, Cardiff University, Cardiff UK. Electronic address: currie@cardiff.ac.uk.
authors: Craig J
authors: CJ
authors: Currie
mesh_terms: D000368:Aged; D002318:Cardiovascular Diseases / Q000453:epidemiology; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007333:Insulin Resistance / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D000077205:Pioglitazone; D012189:Retrospective Studies; D012307:Risk Factors; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D000077205:Pioglitazone; D000077154:Rosiglitazone; D045162:Thiazolidinediones
keywords: Diabetes; Discontinuation; Rosiglitazone