Serious skin and subcutaneous disorders caused by a sodium-glucose co-transporter 2 inhibitor, ipragliflozin

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K06804
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47060:Clinical pharmacy-related
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: Sakaeda Toshiyuki 京都薬科大学, 薬学部, 教授 (00304098)
• Co-Investigator(Kenkyū-buntansha): 西口 工司 京都薬科大学, 薬学部, 教授 (80379437)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: SGLT2阻害剤 / 重篤な皮膚障害 / ipragliflozin

Outline of Final Research Achievements

In Japan, sodium-glucose co-transporter 2 (SGLT2) inhibitors, which are used for the treatment of type 2 diabetes mellitus, have been reported to be associated with serious skin and subcutaneous disorders (SSSD). These events were suggested to be specific for the first inhibitor, ipragliflozin. This study was conducted to elucidate the mechanisms underlying the ipragliflozin-specific SSSD and establish its preventive or therapeutic strategies. Alteration of cytokine pathway by ipragliflozin was suggested in the 3-D human normal skin model consisting of fibroblasts and keratinocytes, but ipragliflozin-specific alterations were not found when fibroblasts or keratinocytes only, suggesting cell-to-cell interaction might be important for the ipragliflozin-specific SSSD. Additionally, concentrative uptake of ipragliflozin into keratinocytes was found in this study, possibly being an important factor, although the transporter remained unclear.

Free Research Field

医療薬学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、SGLT2 阻害剤の適正使用、具体的には、どのSGLT2 阻害剤で重篤な皮膚障害が起こりやすいかに関して情報を提供し、糖尿病の治療における問題の解決の一助となるものであるが、将来的にも、医薬品による重篤な皮膚障害の発症メカニズムの解明並びに予防／治療方法の探索に有用な情報を与えるものである。