Impact of clinical evidence communications and drug regulation changes concerning rosiglitazone on prescribing patterns of antidiabetic therapies

Abstract

Purpose: Cardiovascular safety alerts about rosiglitazone resulted in regulatory actions in several countries in 2010, but the Food and Drug Administration eliminated access restrictions in 2013, reflecting new evidence concerning the drug safety. We investigated the effects of safety signals and regulation shifts concerning rosiglitazone on prescribing of antidiabetic drugs (ADs).

Methods: Patient data were extracted from the Korean health insurance claims database for 2007 to 2015. Linear regression and interrupted time series analyses were performed to examine drug utilization trends and the impact of 5 milestone events regarding rosiglitazone safety on AD utilization.

Results: A steady growth was observed in the AD consumption, with metformin preserving its dominant market share throughout the period. Pioglitazone use has increased since 2008 in response to safety issues surrounding rosiglitazone. A significant decline in rosiglitazone use was observed after Nissen's meta-analysis and safety warnings (2007) and after restriction/suspension of access to rosiglitazone (2010), associated with a drop in prevalence by 29.5%/year and 99.5%/year, respectively. The most common AD newly started among users who discontinued rosiglitazone in 2010 was pioglitazone, followed by dipeptidyl peptidase-4 (DPP-4) inhibitors. Our concomitancy analysis showed that DPP-4 inhibitors have overtaken sulfonylureas since 2014 as the most common add-on to metformin.

Conclusions: The most frequently added AD in diabetes patients who had switched off rosiglitazone in 2010 was pioglitazone, followed by DPP-4 inhibitors. Despite new evidence from a long-term clinical trial and the Food and Drug Administration's subsequent decision to eliminate access restrictions on rosiglitazone in 2013, domestic regulations were left intact; hence, its use remained negligible in Korea.

Keywords: antidiabetic drugs; drug safety; drug utilization; pharmacoepidemiology; thiazolidinediones; type 2 diabetes.