Assessing the Risk Minimization Activity in Risk Management Plans for Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2)

-Analysis Using Japanese Adverse Drug Event Report Database and Real-world Clinical Data-

Abstract

In this study, we evaluated the effect of risk minimization activities in a risk management plan (RMP) formulated for sodium-glucose cotransporter-2 (SGLT2) inhibitors using both the Japanese Adverse Drug Event Report database (JADER) and real-world clinical data. We extracted data from the JADER, which is maintained by the Pharmaceuticals and Medical Devices Agency, from the first quarter of 2004 to the second quarter of 2020. We also used real-world clinical data of the patients who took SGLT2 inhibitors among those who visited or were admitted to Gifu Municipal Hospital from June 2014 to January 2018. We conducted a comparison before and after implementing the risk minimization activities. We compared the reported rate of clinical trials with the reported rate after marketing using the JADER. In addition, we compared the prevalence rate of the clinical trials of SGLT2 inhibitors with that in real clinical data. Furthermore, we compared the onset of side effects (in days) reported in clinical trials recorded in the JADER with that in real clinical data. The pre/post comparison showed a significant increase in the reported rates of increased ketone body, volume depletion, urinary tract infections, and genital infections. A significant decrease in the prevalence rates for hypoglycemia and increased ketone body was also observed. Moreover, the time to onset of side effects was significantly shortened in volume depletion. In conclusion, the risk minimization activities in RMP would contribute to the increased reported rate, decreased prevalence rate, and early detection of side effects.