SGLT2阻害薬のすべて

出版社： 先端医学社
著者：
発行日： 2014-04-30
分野： 薬学  >  薬学一般
ISBN： 9784884079789
電子書籍版： 2014-04-30 （第1版第2刷）
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目次

  • 表紙
  • 序
  • 執筆者一覧
  • 目次
  • [ Part 1 ] 糖輸送体の基礎と創薬の歴史をみる
  • [1] 糖輸送体の基礎を知る
  • はじめに
  • 1. 糖代謝と糖輸送
  • 2. 糖輸送体の種類
  • 1) GLUT
  • 2) SGLT
  • 3. SGLT1とSGLT2
  • 1) 発見の歴史と生理機能
  • 2) 腎尿細管でのグルコース再吸収における機能分担
  • 4. 糖尿病におけるグルコース輸送体の発現変動
  • おわりに
  • [2] SGLTを標的とした薬剤, その開発の歴史と経緯を知る
  • はじめに
  • 1. 糖毒性の重要性
  • 2. フロリジンから経口投与可能なSGLT阻害薬へ
  • 3. プロドラッグとして尿細管に選択的なSGLT阻害薬T - 1095
  • 4. T - 1095によって明らかにされた糖毒性の機序
  • 5. SGLT2選択的阻害薬の開発
  • おわりに
  • [ Part 2 ] SGLT2阻害薬の基礎をみる
  • [1] SGLT2阻害薬の基礎薬理を知る
  • はじめに
  • 1. SGLT阻害薬からSGLT2阻害薬への展開
  • 2. 血糖降下にかかわる作用
  • 3. 血糖降下以外の作用
  • 4. SGLT2阻害薬存在下での糖代謝への影響の有無
  • おわりに
  • [2] SGLT2阻害薬の臨床薬理を探る
  • はじめに
  • 1. SGLTとは
  • 2. これまでに報告されたおもな臨床試験
  • 3. 安全性に関する留意点
  • おわりに
  • [ Part 3 ] SGLT2阻害薬の臨床データをみる
  • SGLT2阻害薬の臨床データをみる - 臨床治験データより -
  • はじめに
  • 1. 単独療法の有効性
  • 2. 併用療法の有効性
  • 1) 経口血糖降下薬との併用療法
  • 2) インスリンとの併用療法
  • 3. 長期投与における有効性
  • 4. 体重低下作用
  • 5. 副次的効果 ( 血圧・脂質 )
  • 1) 血圧
  • 2) 脂質
  • 6. 腎機能障害患者における有効性
  • 7. 低血糖
  • 8. 尿路感染・生殖器感染
  • 9. 忍容性・安全性 ( 注意点 )
  • おわりに
  • [ Part 4 ] SGLT2阻害薬の安全性と服薬アドヒアランスをみる
  • SGLT2阻害薬の安全性と服薬アドヒアランスをみる - 臨床治験データより -
  • はじめに
  • 1. 臨床効果 : 血糖低下作用, 体重減少作用
  • 1) ダパグリフロジン
  • 2) カナグリフロジン
  • 3) イプラグリフロジン
  • 4) その他の薬剤
  • 2. 臨床効果 : 降圧作用・脂質代謝改善作用
  • 3. 副作用と服薬アドヒアランスに影響する因子
  • 1) 低血糖
  • 2) 尿路・生殖器感染症・頻尿
  • 3) 心血管イベント
  • おわりに
  • [ Part 5 ] SGLT2阻害薬への期待と予想される注意点を探る
  • [1] SGLT2阻害薬の血糖降下作用への期待を探る
  • はじめに
  • 1. 新たな糖尿病治療の目標
  • 2. SGLT2阻害薬による血糖降下作用
  • 3. 2型糖尿病患者におけるSGLT2阻害薬の血糖低下効果
  • おわりに
  • [2] SGLT2阻害薬の体重への影響と期待を探る
  • はじめに
  • 1. SGLT2阻害薬
  • 2. SGLT2阻害薬服用下の体重減少をどのようにとらえるか
  • 1) ダパグリフロジン
  • 2) カナグリフロジン
  • 3) イプラグリフロジン
  • 4) ルセオグリフロジン
  • 3. 体重減少に伴う摂食行動への影響はあるか
  • 4. SGLT2阻害薬全体としての臨床効果
  • 5. 安全性について
  • おわりに
  • [3] SGLT2阻害薬による膵β細胞機能保護への期待を探る
  • はじめに
  • 1. 糖毒性によるインスリン分泌不全
  • 2. SGLT2欠損肥満糖尿病マウスにおけるβ細胞代償機構
  • 3. 糖尿病モデル動物におけるSGLT2阻害薬のβ細胞保護効果
  • 4. 臨床試験におけるSGLT2阻害薬のβ細胞への作用
  • おわりに
  • [4] SGLT2阻害薬の作用から予想される最も適する患者像を探る
  • はじめに
  • 1. SGLT2阻害薬の特徴
  • 1) 薬剤作用機序の特異性
  • 2) エネルギー喪失による体重減少
  • 3) 低い低血糖リスク
  • 4) 脱水に関するリスク
  • 5) 腎機能低下症例に対する薬効低下の可能性
  • 6) SGLT2阻害薬による血圧低下作用
  • 7) 尿路・性器感染症および発がんリスク増加に関する懸念
  • 8) SGLT1選択性程度に由来する消化器症状発現への懸念
  • 2. 臨床治験での成績
  • 1) 単独療法
  • 2) 併用療法
  • 3. 処方に適する患者像
  • 4. 今後の展開
  • おわりに
  • [5] SGLT2阻害薬服用時に予想される注意点を探る
  • はじめに
  • 1. SGLT2阻害薬において懸念される副作用
  • 2. SGLT2阻害薬でこれまでに認められている副作用ないしはその危険因子の変化
  • 1) 性器感染・尿路感染
  • 2) 血行動態・電解質の変化
  • 3) 脂質プロファイルの変化
  • 4) 発がんリスク
  • 5) 低血糖
  • 3. これまでの臨床試験では認められていないがSGLT2阻害薬の作用にもとづき懸念される副作用
  • 1) サルコペニア
  • 2) 心血管リスク
  • おわりに
  • [6] SGLT2阻害薬と心血管イベントの関連を探る
  • はじめに
  • 1. 2型糖尿病と心血管イベント
  • 2. SGLT2阻害薬の血糖降下作用
  • 3. SGLT2阻害薬によるCVイベント発症抑制に対する多面的作用
  • 1) 体重への影響
  • 2) 血圧への影響
  • 3) 脂質代謝への影響
  • 4) 尿酸代謝への影響
  • 5) CVイベントへの影響
  • おわりに
  • [7] SGLT2阻害薬と腎機能障害の関連を探る
  • はじめに
  • 1. SGLT2阻害薬の作用機構と腎機能障害
  • 2. 腎機能障害時でもSGLT2阻害薬は有効か ?
  • 3. 腎機能障害時にSGLT2阻害薬の副作用は増加するのか ?
  • 4. 糖尿病性合併症にSGLT2阻害薬は有効か ?
  • おわりに
  • [8] SGLT2阻害薬と尿路感染症の関連を探る
  • はじめに
  • 1. SGLT2阻害薬による尿路感染症の頻度
  • 1) 海外における報告
  • 2) わが国における報告
  • 2. 尿糖は尿路感染症のリスクになるか ?
  • 3. グルコースを尿に添加したin vitro実験データ
  • 4. 糖尿病患者における尿路感染症の頻度
  • おわりに
  • [ Part 6 ] わが国におけるSGLT2阻害薬の位置づけを探る
  • [1] SGLT2阻害薬の登場による糖尿病治療の変化を探る
  • はじめに
  • 1. SGLT2阻害薬
  • 2. SGLT2を阻害することによる危険性はないのか ?
  • 3. 選択的SGLT2阻害薬の臨床的効果
  • 4. 選択的SGLT2阻害薬の安全性
  • 5. SGLT2阻害薬によって糖尿病治療がどのように変化するか ?
  • おわりに
  • [2] 各種糖尿病治療薬の違いからSGLT2阻害薬に求められる役割を探る
  • はじめに
  • 1. 糖尿病治療薬の分類と選択
  • 2. SGLT2阻害薬の位置づけ
  • おわりに
  • [3] 作用の違いから併用の可能性と有用性を探る
  • はじめに - インスリン作用を介さない治療薬としての期待と位置づけ -
  • 1. インスリン分泌促進薬との併用
  • 2. インスリン抵抗性改善薬との併用
  • 3. インクレチン関連薬との併用
  • 4. インスリン製剤との併用
  • 5. 日本人を対象にした臨床試験
  • おわりに
  • [4] SGLT2阻害薬使用時に予想される生活習慣指導の注意点を探る
  • はじめに
  • 1. SGLT2阻害薬の作用機序
  • 2. SGLT2阻害薬の体重減少効果
  • 3. SGLT2阻害薬の体脂肪への作用
  • 4. SGLT2阻害薬使用時の食事療法の意義と栄養状態への影響
  • 5. 高齢者や腎機能低下例における注意点
  • 6. 感染症対策
  • おわりに
  • 索引
  • 奥付

この書籍の参考文献

参考文献のリンクは、リンク先の都合等により正しく表示されない場合がありますので、あらかじめご了承下さい。

本参考文献は電子書籍掲載内容を元にしております。

[ Part 1 ] 糖輸送体の基礎と創薬の歴史をみる

P.18 掲載の参考文献
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5) Tabatabai NM, Sharma M, Blumenthal SS et al : Enhanced expressions of sodium-glucose cotransporters in the kidneys of diabetic Zucker rats. Diabetes Res Clin Pract 83 : e27-e30, 2009
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[ Part 2 ] SGLT2阻害薬の基礎をみる

P.33 掲載の参考文献
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P.39 掲載の参考文献
1) Hediger MA, Coady MJ, Ikeda TS et al : Expression cloning and cDNA sequencing of the Na+/glucose co-transporter. Nature 330 : 379-381, 1987
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2) Kanai Y, Lee WS, You G et al : The human kidney low affinity Na+/glucose cotransporter SGLT2. Delineation of the major renal reabsorptive mechanism for D-glucose. J Clin Jnvest 93 : 397-404, 1994
 
3) Chao EC, Henry RR : SGLT2 inhibition-a novel strategy for diabetes treatment. Nat Rev Drug Discov 9 : 551-559, 2010
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5) Rahmoune H, Thompson PW, Ward JM et al : Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 54 : 3427-3434, 2005
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6) Bailey CJ, Gross JL Pieters A et al : Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin : a randomised, double-blind, placebo-controlled trial. Lancet 375 : 2223-2233, 2010
PubMed
7) Rosenstock J, Aggarwal N, Polidori D et al : Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 35 : 1232-1238, 2012
PubMed
8) Cefalu WT, Leiter LA, Yoon KH et al : Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU) : 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 : 941-950, 2013
PubMed
9) Carlson GF, Tou CK, Parikh S et al : Evaluation of the effect of dapagliflozin on cardiac repolarization : a thorough QT/QTc study. Diabetes Ther 2 : 123-132, 2011
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10) Ring A, Brand T, Macha S et al : The sodium glucose cotransporter 2 inhibitor empagliflozin does not prolong QT interval in a thorough QT (TQT) study. Cardiovasc Diabetol 12 : 70, 2013
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11) 加来浩平, 高野泰樹, 池谷泰明ほか : 新規SGLT2阻害薬Tofogliflozinの日本人2型糖尿病患者における有効性及び安全性の検証-第II/III相臨床試験結果. 糖尿病 56 : S238, 2013
 
12) Tanizawa Y, Araki E, Tobe K et al : Efficacy and safety of tofogliflozin administered for 52 weeks as monotherapy or combined with other oral hypoglycemic agents in Japanese patients with type 2 diabetes. European Association for the Study of Diabetes (EASD) 49th Annual Meeting, Barcelona, September 23-27, 2013
 
13) Inagaki N, Kondo K, Yoshinari T et al : Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes : a randomized, double-blind, placebo-controlled, 12-week study. Diabetes Obes Metab 15 : 1136-1145, 2013
PubMed
14) Kaku K, Inoue S, Matsuoka O et al : Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control : a phase II multicentre, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 15 : 432-440, 2013
PubMed

[ Part 3 ] SGLT2阻害薬の臨床データをみる

P.50 掲載の参考文献
1) Stenlof K, Cefalu WT, Kim KA et al : Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 15 : 372-382, 2013
PubMed
2) Ferrannini E, Ramos SJ, Salsali A et al : Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise : a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 33 : 2217-2224, 2010
PubMed
3) Inagaki N, Kondo K, Yoshinari T et al : Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes : a randornized, double-blind, placebo-controlled, 12-week study. Diabetes Obes Metab 15 : 1136-1145, 2013
PubMed
4) Seino Y, Sasaki T, Fukatsu et al : Luseogliflozin, a SGLT2 inhibitor, improves glycaemic control and reduces body weight as monotherapy up to 52 weeks in Japanese patients with type 2 diabetes mellitus. Diabe tologia 56 (SupPle 1) : S82, 2013
 
5) Strojek K, Yoon KH, Hruba V et al : Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with glimepiride : a randomized, 24-week, double-blind, placebo-controlled trial. Diabetes Obes Metab 13 : 928-938, 2011
PubMed
6) Kovacs CS, Seshiah V, Swallow R et al : Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes : a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab 16 : 147-158, 2014
PubMed
7) Wilding JP, Woo V, Rohwedder K et al : Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin : efficacy and safety over 2 years. Diabetes Obes Metab 16 : 124-136, 2014
PubMed
8) Cefalu WT, Leiter LA, Yoon KH et al : Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU) : 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 : 941-950, 2013
PubMed
9) Bailey CJ, Gross JL, Hennicken D et al : Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin : a randomized, double-blind, placebo-controlled 102-week trial. BMC Med 11 : 43, 2013
PubMed
10) 経口血糖降下薬の臨床評価方法に関するガイドライン [平成22年7月9日薬食審査発0709第1号]
 
11) Haneda M, Seino Y, Sasaki T et al : Luseogliflozin, a SGLT2 inhibitor, as add-on therapy to 5 types of oral antidiabetic drugs improves glycaemic control and reduces body weight in Japanese patients with type 2 diabetes mellitus. Diabetologia 56 (Supple 1) : S384, 2013
 
12) Inagaki N, Seino Y, Sasaki T et al : Luseogliflozin, a selective SGLT2 inhibitor, add on to glimepiride for 52 weeks improves glycaemic control with no major hypoglycaemia in Japanese type 2 diabetes patients. Diabetologia 56 (Supple 1) : S384, 2013
 
13) 河野博道, 数田健一, 吉田哲ほか : 2型糖尿病患者におけるイプラグリフロジンの長期有効性および安全性 : 52週間多施設共同非盲検試験 (IGNITE試験). 糖尿病 56 (Supple 1) : S-155, 2013
 
14) 柏木厚典, 志賀貴紀秋山典子ほか : 2型糖尿病患者におけるイプラグリフロジンと他の経口血糖降下薬との併用 第III相二重盲検並行群間比較試験. 糖尿病 56 (Supple 1) : S-238, 2013
 
15) Bolinder J, Ljunggren O, Johansson L et al : Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab 16 : 159-169, 2014
PubMed
16) Lavalle-Gonzalez FJ, Januszewicz A, Davidson J et al : Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy : a randomised trial. Diabetologia 56 : 2582-2592, 2013
PubMed
17) Rosenstock J, Vico M, Wei L et al : Effects of dapagliflozin, an SGLT2 inhibitor, on HbAlc, body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 35 : 1473-1478, 2012
 
18) Yale JF, Bakris G, Cariou B et al : Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Me tab 15 : 463-473, 2013
 
19) Ferrannini E, Veltkamp SA, Smulders RA et al : Renal glucose handling : impact of chronic kidney disease and sodium-glucose cotransporter 2 inhibition in patients with type 2 diabetes. Diabetes Care 36 : 1260-1265, 2013
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20) Haneda M, Seino Y, Sasaki T et al : Luseogliflozin (TS-071), aselective SGLT2 inhibitor, improves glycemic control in Japanese type 2 diabetic subjects with renal impairment. Diabetologia 55 (Supple 1) : S303, 2012
 
21) Nauck MA, Del Prato S, Meier JJ et al : Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin : a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 34 : 2015-2022, 2011
PubMed
22) Dapagliflozin (Forxiga) : EU summary of product characteristics. Available from : http://www.medicines.org.uk/emc/medicine/27188/SPC/Forxi ga+5%20 mg++%26+10+mg+film+coated+tablets/
 
23) Canagliflozin (lnvokana) : prescribing information. Available from : http://www.invokanahcp.com/prescribing-information.pdf/
 
24) Johnsson KM, Ptaszynska A, Schmitz B et al : Urinary tract infections in patients with diabetes treated with dapagliflozin. J Diabetes Complications 27 : 473-478, 2013
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25) Johnsson KM, Ptaszynska A, Schmitz B et al : Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications 27 : 479-484, 2013
PubMed
26) Kaku K, Inoue S, Matsuoka O et al : Efficacy and safety of dapagliflozin as a monotherapy for type 2 diabetes mellitus in Japanese patients with inadequate glycaemic control : a phase II multicentre, randomized, double-blind, placebo-controlled trial. Diabetes Obes Metab 15 : 432-440, 2013
PubMed

[ Part 4 ] SGLT2阻害薬の安全性と服薬アドヒアランスをみる

P.59 掲載の参考文献
1) List JF, Woo V, Morales E et al : Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 32 : 650-657, 2009
PubMed
2) Wilding Jp, Norwood P, T'Joen C et al : A study of dapagliflozin in patierlts with type 2 diabetes receiving high doses of insulin plus insulin sensitizers : applicability of a novel insulin-independent treatment. Diabetes Care 32 : 1656-1662, 2009
 
3) Bailey CJ, Gross JL, Pieters A et al : Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin : a randomised, double-blind, placebo-controUed trial. Lancet 375 : 2223-2233, 2010
PubMed
4) Bailey CJ, Gross JL, Hennicken D et al : Correction : Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin : a randomized, double-blind, placebo-controlled 102-week trial. BMC Med 11 : 193, 2013
 
5) Bolinder J, Ljunggren O, Kullberg J eta1 : Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97 : 1020-1031, 2012
 
6) Zhang L, Feng Y, List J et al : Dapaglinozin treatment in patients with different stages of type 2 diabetes mellitus : effects on glycaemic control and body weight. Diabetes Obes Metab 12 : 510-516, 2010
 
7) Wilding JP, Woo V, Soler NG et al : Long-term efficacy of dapagliflozin in patients with type 2 diabetes mellitus receiving high doses of insulin : arandomized trial. Ann Intern Med 156 : 405-415, 2012
 
8) Jabbour SA, Hardy E, Sugg J et al : Dapagliflozin Is Effective as Add-on Therapy to Sitagliptin With or Without Metformin : A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Studys. Diabetes Care 37 : 740-750, 2014
PubMed
9) Nauck MA, Del Prato S, Meier JJ et al : Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin : a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 34 : 2015-2022, 2011
PubMed
10) Clar C, Gill JA, Court R et al : Systematic review of SGLT2 receptor inhibitors in dual or triple therapy in type 2 diabetes. . BMf Open 2 : e001007, 2012
PubMed
11) Stenlof K, Cefalu WT, Kim KA et al : Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 15 : 372-382, 2013
PubMed
12) Rosenstock J, Aggarwal N, Polidori D et al : Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metforrnin in sublects with type 2 diabetes. Diabetes Care 35 : 1232-1238, 2012
 
13) Lavalle-Gonzalez FJ, Januszewicz A, Davidson J et al : Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy : a randomised trial. Diabetologia 56 : 2582-2592, 2013
PubMed
14) Wilding JP, Charpentier G, Hollander P et al : Efficacy and safety of canagliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin and sulphonylurea : a randomised trial. Int J Clin Pract 67 : 1267-1282, 2013
PubMed
15) Yale JF, Bakris G, Cariou B et al : Efficacy and safety of canagliflozin in subjects with type 2 diabetes and chronic kidney disease. Diabetes Obes Metab 15 : 463-473, 2013
PubMed
16) Inagaki N, Kondo K, Yoshinari T et al : Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes : a randomized, double-blind, placebo-controlled, 12-week study. Diabetes Obes Metab 15 : 1136-1145, 2013
PubMed
17) Cefalu WT, Leiter LA, Yoon KH et al : Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU) : 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 : 941-950, 2013
PubMed
18) Kashiwagi A, Kazuta K, Yoshida S et al : Randomized, placebo-controlled, double-blind glycemic control trial of novel SGLT2 inhibitor ipragliflozin in Japanese patients with type 2 diabetes mellitus. J Diabetes Investig, in press
 
19) Fonseca VA, Ferrannini E, Wilding JP et al : Active-and placebo-controlled dose-finding study to assess the efficacy, safety, and tolerability of multiple doses of ipragliflozin in patients with type 2 diabetes mellitus. J Diabetes Complications 27 : 268-273, 2013
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20) Wilding Jp, Ferrannini E, Fonseca VA et al : Efficacy and safety of ipragliflozin in patients with type 2 diabetes inadequately controlled on metformin : a dose-finding study. Diabetes Obes Metab 15 : 403-409, 2013
PubMed
21) Inagaki N, Seino Y, Sasaki T et al : Luseogliflozin, a selective SGLT2 inhibitor, added on to glimepiride for 52 weeks improves glycaemic control with no major hypoglycaemia in Japanese type 2 diabetes patients. European Association for the Study of Diabetes (EASD), 49th Annual Meeting 2013 ; OP 31-184
 
22) Seino Y, Sasaki T, Fukatsu A et al : Luseogliflozin, a SGLT2 inhibitor, improves glycaemic control and reduced body weight as monotherapy up to 52 weeks in Japanese patients with type 2 diabetes mellitus. European Association for the Study of Diabetes (EASD), 49th Annual Meeting 2013 ; PS 075-956
 
23) Haneda M, Seino Y, Sasaki T et al : Luseoglinozin, a SGLT2 inhibitor, as add-on therapy to 5 types of oral antidiabetic drugs improves glycaemic control and reduces body weight in Japanese patients with type 2 diabetes mellitus. European Association for the Study of Diabetes (EASD), 49th Annual Meeting 2013 ; PS 075-957
 
24) Araki E, Kaku K, Watada H et al : Verification of the efficacy and safety of tofogliflozin, a novel SGLT2 inhibitor, in Japanese patients with type 2 diabetes mellitus : results from a phase 2/3 clinical study. European Association for the Study of Diabetes (EASD), 49th Annual Meeting 2013 ; PS 073-929
 
25) Tanizawa Y, Araki E, Tobe K et al : Efficacy and safety of tofogliflozin administered for 52 weeks as monotherapy or combined with other oral hypoglycaemic agents in Japanese patients with type 2 diabetes. European Association for the Study of Diabetes (EASD), 49th Annual Meeting 2013 ; OP 31-185
 
26) Ferrannini E, Seman L, Seewaldt-Becker E et al : A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes. Diabetes Obes Metab 15 : 721-728, 2013
PubMed
27) Rosenstock J, Seman LJ, Jelaska A et al : Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia. Diabetes Obes Metab 15 : 1154-1160, 2013
PubMed
28) Ferrannini E, Berk A, Hantel S et al : Long-Term Safety and Efficacy of Empagliflozin, Sitagliptin, and Metformin : An active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes. Diabetes Care 36 : 4015-4021, 2013
PubMed
29) Kovacs CS, Seshiah V, Swallow R et al : Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes : a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab 16 : 147-158, 2014
PubMed

[ Part 5 ] SGLT2阻害薬への期待と予想される注意点を探る

P.67 掲載の参考文献
1) 科学的根拠に基づく糖尿病診療ガイドライン 2013, 日本糖尿病学会編, 南江堂, 2013, pp. 21-30
 
2) 糖尿病治療ガイド 2012-2013 血糖コントロール目標改訂版. 日本糖尿病学会編, 文光堂, 2013, pp. 24-38
 
3) Bailey CJ : Renal glucose reabsorption inhibitors to treat diabetes. Trends Pharmacol Sci 32 : 63-71, 2011
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4) DeFronzo RA, Davidson JA, Del Prato S : The role of the kidneys in glucose homeostasis : a new path towards normalizing glycaemia. Diabetes Obes Metab 14 : 5-14, 2012
PubMed
5) 次世代経口糖尿病治療剤「SGLT2阻害薬」New Current 24 : 2-37, 2013
 
6) Nauck MA, Del Prato S, Meier JJ et al : Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin : arandomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 34 : 2015-2022, 2011
 
P.74 掲載の参考文献
1) Guariguata L et al : Global estimates of diabetes prevalence for 2013 and projections for 2035. Diabetes Res Clin Pract 103 : 137-149, 2014
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2) Washburn WN, Poucher SM : Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs 22 : 463-486, 2013
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3) Mackenzie B, Loo DD, Panayotova-Heiermann M et al : Biophysical characteristics of the pig kidney Na+/glucose cotransporter SGLT2 reveal a common mechanism for SGLT1 and SGLT2. J Biol Chem 271 : 32678-32683, 1996
PubMed
4) Chao EC, Henry RR : SGLT2 inhibition-a novel strategy for diabetes treatment. Nat Rev Drug Discov 9 : 551-559, 2010
PubMed
5) Jurczak MJ, Lee HY, Birkenfeld AL et al : SGLT2 deletion improves glucose homeostasis and preserves pancreatic β-cell function. Diabetes 60 : 890-898, 2011
 
6) Bailey CJ, Gross JL, Pieters A eta1 : Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin : a randomised, double-blind, placebo-controlled trial. Lancet 375 : 2223-2233, 2010
 
7) Zhang L, Feng Y, List J et al : Dapagliflozin treatment in patients with different stages of type 2 diabetes mellitus : effects on glycaemic control and body weight. Diabetes Obes Metab 12 : 510-516, 2010
PubMed
8) Nauck MA, Del Prato S, Meier JJ et al : Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin : a randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 34 : 2015-2022, 2011
PubMed
9) Devenny JJ, Godonis HE, Harvey SJ et al : Weight loss induced by chronic dapaglinozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesitr (Silver Spring) 20 : 1645-1652, 2012
 
10) Macdonald FR, Peel JE, Jones HB et al : The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab 12 : 1004-1012, 2010
PubMed
11) Cefalu WT, Leiter LA, Yoon KH et al : Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU) : 52 week results from a randornised, double-blind, phase 3 non-inferiority trial. Lancet 382 : 941-950, 2013
PubMed
12) Schernthaner G, Gross JL, Rosenstock J et al : Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea : a 52-week randomized trial. Diabetes Care 36 : 2508-2515, 2013
 
13) Liang Y, Arakawa K, Ueta K et al : Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PloS One 7 : e30555, 2012
PubMed
14) List JF, Woo V, Morales E et al : Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 32 : 650-657, 2009
PubMed
15) Hagopian K, Ramsey JJ, Weindruch R : Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver. Exp Gerontol 38 : 267-278, 2003
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16) Jones D : Diabetes field cautiously upbeat despite possible setback for leading SGLT2 inhibitor. Nat Rev Drug Discov 10 : 645-646, 2011
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P.77 掲載の参考文献
1) Butler AE, Janson J, Bonner-Weir S et al : β-cell deficit and increased β-cell apoptosis in humans with type 2 diabetes. Diabetes 52 : 102-110, 2003
 
2) Kaneto H, Miyatsuka T, Kawamori D et al : PDX-1 and MafA play a crucial role in pancreatic β-cell differentiation and maintenance of mature β-cell function. Endocr J 55 : 235-252, 2008
 
3) Prentki M, Nolan CJ : Islet β cell failure in type 2 diabetes. J Clin Invest 116 : 1802-1812, 2006
 
4) Jurczak MJ, Lee HY, Birkenfeld AL et al : SGLT2 deletion improves glucose homeostasis and preserves pancreatic β-cell function. Diabetes 60 : 890-898, 2011
 
5) Macdonald FR, Peel JE, Jones HB et al : The novel sodium glucose transporter 2 inhibitor dapagliflozin sustains pancreatic function and preserves islet morphology in obese, diabetic rats. Diabetes Obes Metab 12 : 1004-1012, 2010
PubMed
6) Liang Y, Arakawa K, Ueta K et al : Effect of canagliflozin on renal threshold for glucose, glycemia, and body weight in normal and diabetic animal models. PLoS One 7 : e30555, 2012
PubMed
7) Tahara A, Kurosaki E, Yokono M et al : Antidiabetic effects of SGLT2-selective inhibitor ipragliflozin in streptozotocin-nicotinamide-induced mildly diabetic mice. J Pharmacol Sci 120 : 36-44, 2012
PubMed
8) Rosenstock J, Aggarwal N, Polidori D et al : Dose-ranging effects of canagliflozin, a sodium-glucose cotransporter 2 inhibitor, as add-on to metformin in subjects with type 2 diabetes. Diabetes Care 35 : 1232-1238, 2012
PubMed
9) Cefalu WT, Leiter LA, Yoon KH et al : Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU) : 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 : 941-950, 2013
PubMed
P.82 掲載の参考文献
1) Bays H : From victim to ally : the kidney as an emerging target for the treatment of diabetes mellitus. Curr Med Res Opin 25 : 671-681, 2009
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2) Hummel CS, Lu C, Loo DD et al : Glucose transport by human renal Na+/d-glucose cotransporters SGLT1 and SGLT2. Am J Physiol Cell Physiol 300 : C14-21, 2011
 
3) Chen LH, Leung PS : Inhibition of the sodium glucose co-transporter-2 : its beneficial action and potential combination therapy for type 2 diabetes mellitus. Diabetes Obes Metab 15 : 392-402, 2013
PubMed
4) Washburn WN, Poucher SM : Differentiating sodium-glucose co-transporter-2 inhibitors in development for the treatment of type 2 diabetes mellitus. Expert Opin Investig Drugs 22 : 463-486, 2013
PubMed
5) Polidori D, Sha S, Ghosh A et al : Validation of a novel method for determining the renal threshold for glucose excretion in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 98 : E867-871, 2013
PubMed
6) DeFronzo RA, Hompesch M, Kasichayanula S et al : Characterization of renal glucose reabsorption in response to dapagliflozin in healthy subjects and subjects with type 2 diabetes. Diabetes Care 36 : 3169-3176, 2013
PubMed
7) Nauck MA, Del Prato S, Meier JJ et al : Dapagliflozin versus glipizide as add-on therapy in patients with type 2 diabetes who have inadequate glycemic control with metformin : arandomized, 52-week, double-blind, active-controUed noninferiority trial. Diabetes Care 34 : 2015-2022, 2011
 
8) Schernthaner G, Gross JL, Rosenstock J et al : Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea : a 52-week randomized trial. Diabetes Care 36 : 2508-2515, 2013
 
9) Kadokura T, Saito M, Utsuno A, Kazuta K et al : Ipragliflozin (ASP1941), a selective sodium-dependent glucose cotransporter 2 inhibitor, safely stimulates urinary glucose excretion without inducing hypoglycemia in healthy Japanese subjects. Diabetol Int 2 : 172-182, 2011
 
10) van den Heuvel LP, Assink K, Willemsen M et al : Autosomal recessive renal glucosuria attributable to amutation in the sodium glucose cotransporter (SGLT2). Hum Genet 111 : 544-547, 2002
 
11) Bolinder J, Ljunggren O, Kullberg J et al : Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97 : 1020-1031, 2012
PubMed
12) Kasichayanula S, Liu X, Pe Benito M et al : The infiuence of kidney function on dapagliflozin exposure, metabolism and pharmacodynamics in healthy subjects and in patients with type 2 diabetes mellitus. Br J Clin Pharmacol 76 : 432-444, 2013
 
13) Zambrowicz B, Ding ZM, Ogbaa I et al : Effects of LX4211, a dual SGLT1/SGLT2 inhibitor, plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes. Clin Ther 35 : 273-285, 2013
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14) Wright EM, Turk E, Martin MG : Molecular basis for glucose-galactose malabsorption. Cell Biochem Biophys 36 : 115-121, 2002
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15) Ferrannini E, Rarnos SJ, Salsali A et al : Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise : arandomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 33 : 2217-2224, 2010
 
16) Wilding JP, Norwood P, T'joen C et al : A study of dapagliflozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers : applicability of a novel insulin-independent treatment. Diabetes Care 32 : 1656-1662, 2009
 
P.87 掲載の参考文献
1) Kim Y, Babu AR : Clinical potential of sodium-glucose cotransporter 2 inhibitors in the management of type 2 diabetes. Diabetes Metab Syndr Obes 5 : 313-327, 2012
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1) Vasilakou D, Karagiannis T, Athanasiadou E et al : Sodium-glucose cotransporter 2 inhibitors for type 2 diabetes : a systematic review and meta-analysis. Ann Intern Med 159 : 262-274, 2013
PubMed
2) Kurosaki E, Ogasawara H : Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes : preclinical and clinical data. Pharmacol Ther 139 : 51-59, 2013
PubMed
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5) Osorio H, Coronel I, Arellano A et al : Sodium-glucose cotransporter inhibition prevents oxidative stress in the kidney of diabetic rats. Oxid Mod Cell Longev 542042, 2012
 
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[ Part 6 ] わが国におけるSGLT2阻害薬の位置づけを探る

P.113 掲載の参考文献
1) Rahmoune H, Thompson PW, Ward JM et al : Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 54 : 3427-3434, 2005
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2) Liu JJ, Lee T, DeFronzo RA et al : Why Do SGLT2 inhibitors inhibit only 30-50% of renal glucose reabsorption in humans? Diabetes 61 : 2199-2204, 2012
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10) Bolinder J, Ljunggren O, Kullberg J et al : Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97 : 1020-1031, 2012
PubMed
11) Schernthaner G, Gross JL, Rosenstock J et al : Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea : a 52-week randomized trial. Diabetes Care 36 : 2508-2515, 2013
 
12) Suzuki M, Honda K, Fukazawa M et al : Tofogliflozin, apotent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice. J Pharmacol Exp Ther 341 : 692-701, 2012
 
P.117 掲載の参考文献
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2) Rahmoune H, Thompson PW, Ward JM et al : Glucose transporter in human renal proximal cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 54 : 3427-3434, 2005
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4) Prentki M, Nolan CJ : lslet β cell failure in type 2 diabetes. J Clin Invest 116 : 1802-1812, 2006
 
5) Schwartz SL, Akinlade B, Klasen S et al : Safety, pharmacokinetic, and pharmacodynamic profiles of ipragliflozin (ASP1941), a novel and selective inhibitor of sodium-dependent glucose co-transporter 2, in patients with type 2 diabetes mellitus. Diabetes Technol Ther 13 : 1219-1227, 2011
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6) Kusaka I, Nagasaka S, Horie H et al : Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients : a possible role in weight stability? Diabetes Obes Metab 10 : 1039-1046, 2008
 
7) New data demonstrate sustained glucose reduction and weight loss up to 90 weeks with investigational SGLT-2 inhibitor, empagliflozin. Study evaluating the efficacy and safety of empagliflozin presented during a late-breaking session at the American Diabetes Association's (ADA) 72nd Scientific Sessions(R)
 
P.125 掲載の参考文献
1) Schernthaner G, Gross JL, Rosenstock J et al : Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with metformin plus sulfonylurea : a 52-week randomized trial. Diabetes Care 36 : 2508-2515, 2013
 
2) Haring HU, Merker L, Seewaldt-Becker E et al : Empagliflozin as add-on to metformin plus sulfonylurea in patients with type 2 diabetes : a 24-week, randomized, double-blind, placebo-controlled trial. Diabetes Care 36 : 3396-3404, 2013
PubMed
3) Cefalu WT, Leiter LA, Yoon KH et al : Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU) : 52 week results from a randomised, double-blind, phase 3 non-inferiority trial. Lancet 382 : 941-950, 2013
PubMed
4) Bailey CJ, Gross JL, Hennicken D et al : Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin : a randomized, double-blind, placebo-controlled 102-week trial. BMC Med 11 : 43, 2013
PubMed
5) Rosenstock J, Vico M, Wei L et al : Effects of dapagliflozin, an SGLT2 inhibitor, on HbA (1c), body weight, and hypoglycemia risk in patients with type 2 diabetes inadequately controlled on pioglitazone monotherapy. Diabetes Care 35 : 1473-1478, 2012
PubMed
6) Kovacs CS, Seshiah V, Swallow R et al : Empagliflozin improves glycaemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients with type 2 diabetes : a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab 16 : 147-158, 2014
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7) Jabbour SA, Hardy E, Sugg J et al : Dapagliflozin is Effective as Add-on Therapy to Sitagliptin With or Without Metformin : A 24-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled Studys. Diabetes Care 37 : 740-750, 2014
PubMed
8) Wilding Jp, Woo V, Rohwedder K et al : Dapaglinozin in patients with type 2 diabetes receiving high doses of insulin : efficacy and safety over 2 years. Disbetes Obes Metab 16 : 124-136, 2014
 
P.130 掲載の参考文献
1) Chao EC, Henry RR : SGLT2 inhibition-a novel strategy for diabetes treatment.Nat Rev Drug Discov 9 : 551-559, 2010
PubMed
2) List JF, Woo V, Morales E et al : Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 32 : 650-657, 2009
PubMed
3) Wilding JP, Norwood P, T'Joen C et al : A study of dapaglinozin in patients with type 2 diabetes receiving high doses of insulin plus insulin sensitizers : applicability of a novel insulin-independent treatment. Diabetes Care 32 : 1656-1662, 2009
 
4) Wilding JP, Woo V, Rohwedder K et al : Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin : efficacy and safety over 2 years. Diabetes Obes Metab 16 : 124-136, 2014
PubMed
5) Bolinder J, Ljunggren O, Kullberg J et al : Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 97 : 1020-1031, 2012
PubMed
6) Bolinder J, Ljunggren O, Johansson L et al : Dapagliflozin maintains glycaemic corltrol while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab 16 : 159-169, 2014
PubMed
7) Inagaki N, Kondo K, Yoshinari T et al : Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes : a randomized, double-blind, placebo-controlled, 12-week study. Diabetes Obes Metab 15 : 1136-1145, 2013
PubMed
8) Devenny JJ, Godonis HE, Harvey SJ et al : Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats. Obesity (Silver Spring) 20 : 1645-1652, 2012
PubMed
9) Johnsson KM, Ptaszynska A, Schmitz B et al : Urinary tract infections in patients with diabetes treated with dapaglinozin. J Diabetes Complications 27 : 473-478, 2013
PubMed
10) Johnsson KM, Ptaszynska A, Schmitz B et al : Vulvovaginitis and balanitis in patients with diabetes treated with dapagliflozin. J Diabetes Complications 27 : 479-484, 2013
PubMed

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