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Title SGLT2阻害薬の心保護作用とメカニズム
Subtitle 総説
Authors 桑原宏一郎
Authors (kana)
Organization 信州大学医学部 循環器内科学
Journal Therapeutic Research
Volume 43
Number 4
Page 283-293
Year/Month 2022 / 4
Article 報告
Publisher ライフサイエンス出版
Abstract 「要約」ナトリウムグルコース共輸送体2(Sodium-Glucose Cotransporter-2:SGLT2)阻害薬は, 腎臓近位尿細管に発現するSGLT2を介した原尿からのグルコース再吸収を抑制し, 血中グルコース濃度を低下させる. 当初糖尿病治療薬として開発されたが, 2型糖尿病患者を対象にした心血管アウトカム試験EMPA-REG OUTCOME試験, CANVASプログラム, DECLARE-TIMI58試験において, SGLT2阻害薬であるエンパグリフロジン, カナグリフロジン, ダパグリフロジンは一貫して心不全による入院リスクを低下させた. その後, 左室駆出率が低下した心不全(Heart Failure with reduced Ejection Fraction:HFrEF)患者を対象に実施されたDAPA-HF試験およびEMPEROR-Reduced試験において, ダパグリフロジンおよびエンパグリフロジンは, 2型糖尿病の有無にかかわらず心血管アウトカムを改善することが示された. 現在, 上記2つの薬剤は慢性心不全治療薬として承認され, 国内外のガイドラインでクラスIに位置づけられている. これと並行して, さまざまな臨床および基礎研究を通じたメカニズム研究により, SGLT2阻害薬の多面的な作用がその心不全発症・進展抑制, 予後改善に関与することが示されている. 特に重要な役割を果たしていると考えられるメカニズムは(1)利尿作用, (2)交感神経の調節作用, (3)心筋エネルギー代謝改善作用, および(4)腎保護作用である. これらの複合的な作用により, 心臓の負荷軽減, 器質的/機能的改善が促され, 臨床試験で認められたような早期からの心不全予後改善作用につながっていると考えられる.
Practice 臨床医学：一般
Keywords SGLT2阻害薬, 心不全, 心筋逆リモデリング, 作用機序
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