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GLP-1受容体作動薬およびGIP/GLP-1受容体作動薬について GLP-1（Glucagon-Like Peptide-1）受容体作動薬およびGIP/GLP-1受容体作動薬は主に2型糖尿病の治療に用いられる注射薬および一部経口薬です。 1．作用機序 GLP-1受容体作動薬：膵臓のβ細胞膜上にあるGLP-1受容体に結合し、インクレチンホルモンであるGLP-1の作用を増強します。これにより、以下の効果を発揮します。・血糖依存性のインスリン分泌促進：血糖値が高い時にインスリンの分泌を促します。・グルカゴン分泌抑制：血糖値を上げる作用のあるグルカゴンの分泌を抑制します。・胃内容物排出遅延作用：食後の血糖値の急激な上昇を抑えます。・食欲抑制作用：体重減少効果に寄与します。 GIP/GLP-1受容体作動薬（チルゼパチドなど）：GLP-1受容体に加え、もう一つのインクレチンホルモンであるGIP（グルコース依存性インスリン分泌刺激ポリペプチド）の受容体にも結合し、両方の作用を増強することで、より強力な血糖降下作用や体重減少作用が期待されます。 2．主な効果と特徴・血糖コントロール改善：空腹時血糖値と食後血糖値の両方を低下させます。・体重減少効果：食欲抑制作用や胃内容物排出遅延作用により、多くの患者さんで体重の低下が期待できます。・低血糖リスク：単独使用では低血糖をきたす可能性は低いです（血糖依存的に作用するため）。・心血管・腎保護効果：一部のGLP-1受容体作動薬には、心血管イベントのリスクを低減する効果や、腎症の進行を抑制する効果が大規模臨床試験で示されています。・投与方法：多くは皮下注射製剤で、1日1～2回投与のものや週1回投与のものがあります。経口薬（セマグルチド）も利用可能です。 3．主な副作用・消化器症状：投与初期に悪心、嘔吐、下痢、便秘などの胃腸障害が比較的多く認められます。多くは一過性ですが、症状が強い場合は医師に相談が必要です。1日1回または2回注射の製剤では、低用量から開始し、徐々に増量することでリスクを軽減します。・注射部位反応：注射薬の場合、注射部位に発赤、腫れ、かゆみなどが起こることがあります。・急性膵炎：まれですが、急性膵炎の報告があります。持続的な激しい腹痛（嘔吐を伴うこともある）などの初期症状に注意が必要です。・胆石症、胆嚢炎：報告があります。・甲状腺髄様癌（動物実験での報告）：ヒトでの関連は不明ですが、甲状腺髄様癌の既往のある患者さんや家族歴のある患者さんには慎重な投与が考慮されます。 4．使用上の注意点・適応：主に2型糖尿病患者さんに用いられ、1型糖尿病やインスリン依存状態の患者さんへの適応はありません。・DPP-4阻害薬との併用：作用機序が類似しているため、原則として併用しません。・SU薬・インスリンとの併用：低血糖のリスクが増加するため、これらの薬剤の用量を減らすことを検討する必要があります。・インスリン治療からの切り替え：インスリン依存状態にないことを確認した上で慎重に行う必要があります。・急性膵炎の既往：膵炎の既往のある患者さんには慎重に投与します。急性膵炎の初期症状について患者さんに十分指導しておく必要があります。・経口セマグルチドの服用方法：1日のうちの最初の食事または飲水の前に、空腹の状態でコップ約半分の水（約120mL以下）とともに1錠服用し、服用後少なくとも30分は飲食および他の薬剤の経口摂取を避けるなど、多くの留意点があります。・GIP/GLP-1受容体作動薬（チルゼパチドなど）の網膜症への影響：急激な血糖コントロールの改善に伴い、糖尿病網膜症が一時的に悪化または顕在化することがあるため、増殖網膜症などを合併する患者さんでは、眼科医と連携し慎重に経過を観察する必要があります。主な薬剤 GLP-1受容体作動薬（注射薬）：・1日1～2回投与：リラグルチド（販売名：ビクトーザ）など・週1回投与：デュラグルチド（販売名：トルリシティ）、セマグルチド（販売名：オゼンピック）など GLP-1受容体作動薬（経口薬）：・セマグルチド（販売名：リベルサス） GIP/GLP-1受容体作動薬（注射薬）：・チルゼパチド（販売名：マンジャロ）これらの薬剤は、血糖降下作用に加えて体重減少効果や心血管・腎保護効果も期待できる場合があり、2型糖尿病治療における重要な選択肢となっていますが、消化器症状などの副作用や使用上の注意点をよく理解し、医師の指示に従って適切に使用することが大切です。