Department of Medicine, Queen's University, Kingston Health Sciences Centre, Kingston, Ontario, Canada.
Curr Opin Nephrol Hypertens. 2021 May 1;30(3):361-368. doi: 10.1097/MNH.0000000000000703.
The benefits of sodium/glucose cotransporter 2 (SGLT2) inhibitors seem to extend beyond glycemic control. We review recent randomized trial evidence evaluating SGLT2 inhibition in nondiabetic settings, including in patients with chronic kidney disease (CKD) and heart failure (HF).
DAPA-CKD, DAPA-HF and EMPEROR-Reduced compared SGLT2 inhibitors to placebo, enrolling 5868 patients without diabetes. In DAPA-CKD, patients with an estimated glomerular filtration rate (eGFR) of 25-75 ml/min/1.73 m2 and macroalbuminuria irrespective of kidney disease aetiology had improved cardiovascular and kidney outcomes if randomized to receive SGLT2 inhibitors (primary composite endpoint: hazard ratio [HR] 0.61, 95% CI 0.51-0.72; absolute risk reduction [ARR] 5.3%). In DAPA-HF and EMPEROR-Reduced, participants with reduced ejection fraction (HFrEF) had improved cardiovascular outcomes when an SGLT2 inhibitor was added to guideline-directed medical therapy, mainly through a reduction in HF hospitalizations (HR 0.70, 95% CI 0.59-0.83; ARR 3.7% and HR 0.69, 95% CI 0.59-0.81; ARR 5.1% with dapagliflozin and empagliflozin, respectively). In all 3 trials, the benefits were not modified by diabetes, baseline eGFR or proteinuria.
SGLT2 inhibitors improve kidney and HF outcomes in patients with high-risk CKD and HFrEF, irrespective of diabetes. Clinicians should become more comfortable prescribing these medications as we await studies that may further broaden their indications.
钠-葡萄糖协同转运蛋白 2（SGLT2）抑制剂的益处似乎不仅限于血糖控制。我们综述了最近评估 SGLT2 抑制剂在非糖尿病患者中的随机试验证据，包括慢性肾脏病（CKD）和心力衰竭（HF）患者。
DAPA-CKD、DAPA-HF 和 EMPEROR-Reduced 试验将 SGLT2 抑制剂与安慰剂进行了比较，共纳入了 5868 名无糖尿病的患者。在 DAPA-CKD 试验中，无论肾病病因如何，肾小球滤过率（eGFR）为 25-75ml/min/1.73m²且伴有大量白蛋白尿的患者，如果随机接受 SGLT2 抑制剂治疗，其心血管和肾脏结局得到改善（主要复合终点：风险比 [HR]0.61，95%CI0.51-0.72；绝对风险降低 [ARR]5.3%）。在 DAPA-HF 和 EMPEROR-Reduced 试验中，射血分数降低（HFrEF）的患者在接受 SGLT2 抑制剂联合指南指导的药物治疗后，心血管结局得到改善，主要通过减少 HF 住院（HR0.70，95%CI0.59-0.83；ARR3.7%和 HR0.69，95%CI0.59-0.81；分别用达格列净和恩格列净时 ARR5.1%）。在所有 3 项试验中，糖尿病、基线 eGFR 或蛋白尿均未改变获益。
SGLT2 抑制剂可改善高危 CKD 和 HFrEF 患者的肾脏和 HF 结局，无论是否患有糖尿病。由于我们正在等待可能进一步扩大这些药物适应证的研究，因此临床医生应更加愿意开这些药物。
