Risk of Myopathy Associated With DPP-4 Inhibitors in Combination With Statins: A Disproportionality Analysis Using Data From the WHO and French Spontaneous Reporting Databases

Recently, a pharmacovigilance safety warning was released by the European Medicines Agency concerning the risk of myopathy and rhabdomyolysis associated with the use of dipeptidyl peptidase 4 (DPP-4) inhibitors (1,2). The warning was based on several cases in which DPP-4 inhibitors were used in association with statins; a drug-drug interaction was suggested (3). As statin use is likely to be common in patients with diabetes, it is important to investigate this potential serious risk and the underlying drug-drug interaction hypothesis. This need is enforced by the recent marketing in several countries of fixed combinations containing both statins and DPP-4 inhibitors (4). The aim of the study, therefore, was to assess the association between myopathy and the use of DPP-4 inhibitors, alone and in combination with statins, by analyzing data from two pharmacovigilance spontaneous reporting databases. Data from the French Base Nationale de Pharmacovigilance (BNPV) and the World Health Organization (WHO) global individual case safety reports database, VigiBase, were analyzed for the 2009–2015 time period. Cases consisted of all reported adverse drug reactions (ADRs) of muscular injury, which were identified in both databases by using the dedicated Standardized MedDRA Queries (“myopathy/rhabdomyolysis”). All reports of other ADRs were considered noncases. The exposures of interest were the use of DPP-4 inhibitors along with statins at the time the ADR occurred, as we were investigating a potential drug-drug interaction between DPP-4 inhibitors and statins. We conducted complementary analyses considering exposures to all noninsulin antidiabetes agents other than DPP-4 inhibitors and to fibrates. As other noninsulin antidiabetes agents share indications with DPP-4 inhibitors, the …