２型糖尿病：SGLT2薬剤間差？

システマティックレビュー・メタアナリシスなので、新しいRCTなど含まないかもしれないので、逐一情報アップデート必要だろう


個人的なまとめだと

• HbA1ｃ指標改善だと、ジャディアンス、カナグル
• 腎機能低下への懸念あるのは、ルセフィー、懸念乏しいのはスーグラ、フォシーガ、カナグル
• 体重減少作用は薬剤間差が明瞭でなく
• 死亡率や重大心血管イベントに関してはより緩やかなアウトカムにのみ有意性を認める

Efficacy and Safety of sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes and moderate renal function impairment: A Systematic Review and Meta-Analysis

Lin Zhang, et al.
Diabetes Research and Clinical Practice 
DOI: https://doi.org/10.1016/j.diabres.2018.03.047

HbA1c

In patients with moderate renal function impairment (stage 3 CKD), SGLT2 inhibitors (n=2062) showed significant improvement in HbA1c compared with the placebo (n=1115) (WMD, -0.23%; 95% CI: -0.38 to -0.08) (Fig. 3) (I2 = 52.9%; P= 0.048).

As for each SGLT2 inhibitor, compared with the placebo,
empagliflozin ＜ジャディアンス＞ (mean: -0.44%, 95% CI:-0.61 to -0.27[11]; -0.19%, 95% CI:-0.33 to -0.05[16])
canagliflozin ＜カナグル＞300 mg once daily (-0.41%,95% CI: -0.68, -0.14)[15] notably reduced HbA1c; 

but not ipragliflozin＜スーグラ＞[13], luseogliflozin[＜ルセフィー＞12], dapagliflozin＜フォシーガ＞[14] or ertugliflozin[17].

腎機能

Four studies reported a change of renal function during the trials[12-15] in patients with moderate renal function impairment.
Treatment with SGLT2 inhibitors (n=379) led to the reduction of eGFR compared with the placebo (n=178) (WMD, -1.74ml/min/1.73m2; 95% CI: -3.45 to -0.03) (I2 = 0%; P = 0.567) (Fig. 5).
As for each SGLT2 inhibitor, compared with the placebo,

ipragliflozin[13] (WMD, -2.00 ml/min/1.73m2; 95% CI: -4.52 to 0.52),
dapagliflozin[14] (WMD, -0.32 ml/min/1.73m2; 95% CI: -2.83 to 2.19)
canagliflozin[15] (WMD, -1.52 ml/min/1.73m2; 95% CI: -3.45 to 0.41) did not result in the reduction of eGFR,
unlike luseogliflozin (WMD, -2.50 ml/min/1.73m2; 95% CI: -4.27 to -0.73)[12].

死亡率・心血管系イベント

All-cause mortality was reported in five articles [11, 14-17].
The rate of all-cause mortality was 6.4% and 7.5% in SGLT2 inhibitors and placebo groups, respectively, there was no difference (RR, 0.79; 95% CI: 0.54 to 1.15) (I2 = 0%; P = 0.872) (Fig. S4).
Cardiovascular outcomes were reported in one article [16]. In SGLT2 inhibitors and placebo groups, 3-point major adverse cardiovascular events (MACE): composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke, were similar (hazard ratio [HR], 0.88; 95%CI: 0.69, 1.13), both of the hospitalization for heart failure (HR, 0.59; 95%CI:0.39, 0.88) and all-cause hospitalization (HR, 0.83; 95CI%:0.72, 0.95) were lower.

体重

Six studies [11-16] described a change in body weight in patients with moderate renal impairment. In patients with moderate renal function impairment, treatment with SGLT2 inhibitors (n=1823) resulted in an obvious reduction in body weight compared to the placebo (n=999) (WMD, -1.45kg; 95% CI: -2.01 to -0.89) (I2=42.9%; P=0.119) (Fig. S5).
As presented in Fig. S5, all of the included SGLT2 inhibitors brought about significant body weight reduction.

---

EMPA-REG OUTCOME以降、ジャディアンス主体にSGLT-2選別しているが、ちょっと冷静になる必要があるかも・・・