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

Abstract

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.

Durability of initial antidiabetic monotherapy and subsequent treatment adjustment patterns among newly treated type 2 diabetes patients

“…Over the last decade, DPP-4 inhibitors have achieved a substantial uptake in prescription volume, and they have overtaken SUs as the most preferred add-on to metformin since 2014 in Korea. 3 In the current analysis, among incident users of DPP-4 inhibitors, a tendency more toward treatment addition rather than switches to alternative therapy was observed, which could be understood in the context of their favorable safety and tolerability profile. Despite the growing preference for DPP-4 inhibitors in clinical practice, in our analysis, they were evaluated as inferior to metformin in delaying the first-treatment adjustment when used as initial monotherapy.…”

“… 20 Of note is that TZD agents analyzed in our study were primarily pioglitazone as rosiglitazone’s use became almost nonexistent post the severe access restrictions on the latter TZD agent in late 2010 in Korea due to increased, albeit controversial, CV risk. 3 TZD therapy may improve insulin sensitivity and reduce the rate of decline in β-cell function, and these features might be effective in delaying monotherapy failure by positively influencing the durability of the therapeutic effect. 7 , 21 Nevertheless, the findings in the present study did not support the durability of TZD-based initial monotherapy as demonstrated in the previous study.…”

“…The year 2011 was chosen as the start of the index period considering a series of safety alerts regarding rosiglitazone’s CV risks issued from 2007 onward until the heavy access restrictions imposed on the TZD agent in late 2010, which substantially affected the use rates of TZDs. 3 To ensure that we selected the patients tolerating their initial antidiabetic therapy, we restricted our analyses to only those with initial treatment duration of at least 90 consecutive days. Patients with duration of antidiabetic therapy <365 days since the commencement of their initial therapy were excluded.…”

“…1 , 2 Thanks to several novel hypoglycemic agents newly approved for clinical use over the last decades, prescribers and patients now have a wide variety of therapeutic options to choose from for treatment escalation or switching. 3 Despite the accumulating evidence on the efficacy and safety of newly available antidiabetic drugs (ADs), clinical trials in the past were conducted primarily focusing on intermediate physiological outcomes, such as hemoglobin A1c, with cardiovascular (CV) outcomes under investigation only recently. 4 – 6 …”

Dysregulation of NRF2 in Cancer: from Molecular Mechanisms to Therapeutic Opportunities

“…However, the mechanisms by which DPP-4 inhibitors induce NRF2 activity are largely unknown. Considering that they have largest prescription volume among the new antidiabetic drug classes ( Ahren, 2008 ; Phung et al ., 2010 ; Noh et al ., 2017 ), the recent findings regarding their potential NRF2-modulatory effects are of significant importance for patients with diabetes who are chronically exposed to the respective antidiabetic therapy and who are at increased risk of developing malignant complications because of underlying disease. Although the mechanisms of DPP-4 inhibitors’ effects on NRF2 activation remain elusive, it might be beneficial to use a DPP-4 inhibitor in combination with metformin in diabetes patients who also have cancer as a comorbidity.…”