Antidiabetic prescribing trends and predictors of thiazolidinedione discontinuation following the 2007 rosiglitazone safety alert☆
Introduction
Considerable public attention was generated by the Nissen and Wolski meta-analysis, published online 21 May 2007, which associated rosiglitazone with a significant increase in the risk of myocardial infarction compared to placebo or other antidiabetic medications [1]. A smaller meta-analysis using patient-level data and retrospective event review conducted by the manufacturer showed a similar increased risk of myocardial ischemia with rosiglitazone [2]. In response, the U.S. Food and Drug Administration (FDA) issued an Information for Healthcare Professionals that warned of the potential risk of ischemic cardiovascular events in patients taking rosiglitazone [3]. The FDA convened a joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee on 30 July 2007 to further evaluate rosiglitazone safety data. The committee members concluded that despite evidence associating rosiglitazone with increased cardiac ischemic risk, the overall risk-benefit profile supported its continued marketing in the United States [4]. In contrast, a randomized controlled trial and meta-analyses demonstrated neutral or beneficial effect on cardiovascular risk with pioglitazone therapy [5], [6], [7]. On 14 August 2007, a black box warning was added to prescribing information for both TZDs regarding their potential to cause or exacerbate heart failure [8], [9]. An additional black box warning was added to rosiglitazone labeling on 19 November 2007 indicating that rosiglitazone has been associated with an increased risk of myocardial ischemic events by meta-analysis, but available data are inconclusive [9]. Despite the publication of several studies including a randomized controlled trial, the cardiovascular risks of rosiglitazone have not been definitively established [10], [11], [12], [13], [14], [15], [16]. However, expert consensus regards the cardiovascular risk of rosiglitazone to be greater than that of pioglitazone [17]. On September 23, 2010, the FDA announced their decision to require a Risk Evaluation and Mitigation Strategy for rosiglitazone, which will limit its availability [18].
The rosiglitazone case provides insight into the impact of medication safety warnings on prescribing patterns. This may have implications for manner by which the FDA, medical and lay media disseminate information. Previous studies describing trends in TZD prescribing surrounding the 2007 safety concerns have not examined large, continuous cohorts of both pioglitazone and rosiglitazone users. Further, the prescribing trends for other antidiabetic medications surrounding the advisory have not been elucidated.
The objectives of the current study are to determine the change in antidiabetic medication prescribing patterns and predictors of TZD discontinuation in a cohort of TZD users six months following the 2007 FDA rosiglitazone safety alert.
Section snippets
Methods
This study was a retrospective analysis of health insurance claims data using a pre-post design. Changes in medication use for patients receiving either rosiglitazone or pioglitazone were compared immediately before and six months after the safety alert.
Results
We identified 146,495 individuals with a current prescription for either rosiglitazone or pioglitazone on the FDA safety alert date. Of these, 78,019 (53.3%) were continuously enrolled for all of 2006 and 2007 and had a previous prescription for the TZD in 2007. The final study population included 40,836 individuals prescribed rosiglitazone and 37,183 prescribed pioglitazone. Baseline characteristics of study cohorts are displayed in Table 1. Insurance plan type was not available for 1092
Discussion
The present investigation was conducted to determine antidiabetic prescribing trends and predictors of TZD discontinuation shortly after the 2007 FDA safety alert. In our large cohort of patients prescribed rosiglitazone on the day of the alert, over half discontinued therapy six months later. This was true for less than one-quarter of patients previously prescribed pioglitazone. A substantial minority of patients who discontinued rosiglitazone were switched to pioglitazone. The black box
Conflict of interest
There are no conflicts of interest.
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Trends in global prescribing of antidiabetic medicines in primary care: A systematic review of literature between 2000–2018
2019, Primary Care DiabetesCitation Excerpt :A few years later rosiglitazone and pioglitazone was introduced to the market as manufacturers proved this drug not to cause liver toxicity. However safety alerts about increased cardiovascular risk [59–61] resulting in reduced number of new users of the two drugs. Currently availability of these drugs are altered or limited in some European countries.
Drug safety and the impact of drug warnings: An interrupted time series analysis of diabetes drug prescriptions in Germany and Denmark
2016, Health PolicyCitation Excerpt :For the United States, mixed effects of drug warnings from the Food and Drug Administration (FDA) by drug class were found for pain medication [5]. In the domain of diabetes, where side-effects are frequent, several US-based studies assessed the prescription pattern of glucose-lowering drugs for a short period around the publication of the FDA safety alert for the substance rosiglitazone in May 2007 [6–9]. For Europe, studies from the Netherlands and the UK, which analysed changes in prescribing behaviour after the drug warnings were made and switching of drug regimens by prescribers, found a decline in prescriptions for rosiglitazone [10–12].
How Did Multiple FDA Actions Affect the Utilization and Reimbursed Costs of Thiazolidinediones in US Medicaid?
2015, Clinical TherapeuticsCitation Excerpt :On August 14, 2007, a boxed warning was added to the prescribing information for thiazolidinediones (rosiglitazone and pioglitazone) regarding their potential to cause or exacerbate heart failure.16–19 However, expert consensus was that the cardiovascular risk of rosiglitazone was greater than that of pioglitazone.4,13 After completion of GlaxoSmithKline’s RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycaemia in Diabetes) randomized clinical trial,20 the FDA met again in September 2010 to review emerging data, including the final results of the RECORD trial, updated meta-analyses conducted separately by the FDA and other independent researchers, and a series of observational studies comparing rosiglitazone and pioglitazone.11,14,21–23
The effect of withdrawal of rosiglitazone on treatment pathways, diabetes control and patient outcomes: A retrospective cohort study
2014, Journal of Diabetes and its ComplicationsCitation Excerpt :Furthermore, these patients may also have been considered at lower risk of MI by their physicians compared to those patients who were discontinued following the initial cardiovascular warnings of 2007. A study from the USA has shown that patients with pre-existing cardiovascular co-morbidity were more likely to have rosiglitazone withdrawn following the initial health warnings (Hurren et al., 2011). To allow for this in our comparative analyses, pioglitazone controls had to have had a minimum exposure equal to that of the rosiglitazone case.
Safety of Exenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Treated With a Thiazolidinedione Alone or in Combination With Metformin for 2 Years
2012, Clinical TherapeuticsCitation Excerpt :TZD use has been associated with peripheral edema and heart failure, and meta-analyses have reported an increased risk of myocardial infarction and cardiovascular-related death associated with the TZD rosiglitazone.12,15 These observations have resulted in a decline in the use of TZDs for the treatment of T2DM.26–28 In the present study, no cases of heart failure or myocardial infarction, and few cases of mild edema, were reported.
The friday effect: Firm lobbying, the timing of drug safety alerts, and drug side effects
2020, Management Science
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These data were partially presented at the 70th Scientific Sessions of the American Diabetes Association in Orlando, FL, June 2010.