カナグリフロジンは複合エンドポイントを減らすが、下肢切断リスクには注意が必要。

■ 試験デザイン
TPECOに分けると下記のようになります
T RCT 188.2weeks
P 2型糖尿病患者&心血管高リスク n=10,142
E カナグリフロジン
C プラセボ
O 
複合エンドポイント
=心臓血管死 + 非致死的心筋梗塞   + 非致死的脳卒中



■ 結果

The rate of the primary outcome was lower with canagliflozin than with placebo (occurring in 26.9 vs. 31.5 participants per 1000 patient-years; hazard ratio, 0.86; 95% confidence interval [CI], 0.75 to 0.97; P<0.001 for noninferiority; P=0.02 for superiority). Although on the basis of the prespecified hypothesis testing sequence the renal outcomes are not viewed as statistically significant, the results showed a possible benefit of canagliflozin with respect to the progression of albuminuria (hazard ratio, 0.73; 95% CI, 0.67 to 0.79) and the composite outcome of a sustained 40% reduction in the estimated glomerular filtration rate, the need for renal-replacement therapy, or death from renal causes (hazard ratio, 0.60; 95% CI, 0.47 to 0.77).

■ 副作用

Adverse reactions were consistent with the previously reported risks associated with canagliflozin except for an increased risk of amputation (6.3 vs. 3.4 participants per 1000 patient-years; hazard ratio, 1.97; 95% CI, 1.41 to 2.75); amputations were primarily at the level of the toe or metatarsal

プラセボですら1000人年に3.4の下肢切断リスクがあるのは、日本とは異なりそうではあるものの、エンパグリフロジンと比較すると、これはなかなか厳しい所。
一応他のSGLT2阻害薬を使う場合も下肢リスクに注意しながら使うこととしましょう。



■ 参照文献
Neal B. et al., N Engl J Med. 2017 Jun 12.
PMID: 28605608