The effect of withdrawal of rosiglitazone on treatment pathways, diabetes control and patient outcomes: a retrospective cohort study.

Aims: 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.

Conclusion: Withdrawal of rosiglitazone was associated with worsening glucose control and subsequent intensification of treatment regimen.