Seidu Samuel, Kunutsor Setor K, Cos Xavier, Gillani Syed, Khunti Kamlesh
Leicester Diabetes Centre, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK; Diabetes Research Centre, University of Leicester, Leicester General Hospital, Gwendolen Road, Leicester LE5 4WP, UK.
Translational Health Sciences, Bristol Medical School, University of Bristol, Southmead Hospital, Learning and Research Building (Level 1) Bristol, UK; National Institute of Health Research, Bristol Biomedical Research Centre, University of Bristol, Bristol, UK.
Prim Care Diabetes. 2018 Jun;12(3):265-283. doi: 10.1016/j.pcd.2018.02.001. Epub 2018 Feb 24.
Sodium-glucose co-transporter 2 (SGLT2) inhibitors may have renal protective effects in people with impaired kidney function. We assessed the use of SGLT2 inhibitors in people with type 2 diabetes with or without renal impairment [defined as estimated glomerular filtration rate (eGFR) of ≥30 and <60ml/min/1.73m and/or UACR>300 and ≤5000mg/g] by conducting a systematic review and meta-analysis of available studies.
Randomised controlled trials (RCTs) were identified from MEDLINE, EMABASE, Web of Science, the Cochrane Library, and search of bibliographies to March 2017. No relevant observational study was identified. Summary measures were presented as mean differences and narrative synthesis performed for studies that could not be pooled.
42 articles which included 40 RCTs comprising 29,954 patients were included. In populations with renal impairment, SGLT2 inhibition compared with placebo was consistently associated with an initial decrease in eGFR followed by an increase and return to baseline levels. In pooled analysis of 17 studies in populations without renal impairment, there was no significant change in eGFR comparing SGLT2 inhibitors with placebo (mean difference, 0.51ml/min/1.73m; 95% CI: -0.69, 1.72; p=403). SGLT2 inhibition relative to placebo was associated with preservation in serum creatinine levels or initial increases followed by return to baseline levels in patients with renal impairment, but levels were preserved in patients without renal impairment. In populations with or without renal impairment, SGLT2 inhibitors (particularly canagliflozin and empagliflozin) compared with placebo were associated with decreased urine albumin, improved albuminiuria, slowed progression to macroalbuminuria, and reduced the risk of worsening renal impairment, the initiation of kidney transplant, and death from renal disease.
Emerging data suggests that with SGLT2 inhibition, renal function seems to be preserved in people with diabetes with or without renal impairment. Furthermore, SGLT2 inhibition prevents further renal function deterioration and death from kidney disease in these patients.
钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂可能对肾功能受损的患者具有肾脏保护作用。我们通过对现有研究进行系统评价和荟萃分析，评估了SGLT2抑制剂在有或无肾功能损害（定义为估计肾小球滤过率[eGFR]≥30且<60ml/min/1.73m²和/或尿白蛋白肌酐比值[UACR]>300且≤5000mg/g]）的2型糖尿病患者中的应用情况。
从MEDLINE、EMABASE、科学引文索引、考克兰图书馆以及截至2017年3月的文献目录检索中识别随机对照试验（RCT）。未识别到相关观察性研究。汇总测量指标以均值差异表示，并对无法合并的研究进行叙述性综合分析。
纳入了42篇文章，其中包括40项RCT，共29954例患者。在肾功能损害人群中，与安慰剂相比，SGLT2抑制始终与eGFR最初下降随后上升并恢复至基线水平相关。在对17项无肾功能损害人群研究的汇总分析中，与安慰剂相比，SGLT2抑制剂组的eGFR无显著变化（均值差异为0.51ml/min/1.73m²；95%置信区间：-0.69，1.72；p = 0.403）。与安慰剂相比，SGLT2抑制与肾功能损害患者血清肌酐水平保持或最初升高随后恢复至基线水平相关，但在无肾功能损害患者中水平保持稳定。在有或无肾功能损害的人群中，与安慰剂相比，SGLT2抑制剂（尤其是卡格列净和恩格列净）与尿白蛋白减少、白蛋白尿改善、向大量白蛋白尿进展减缓以及肾功能恶化、肾移植起始和肾病死亡风险降低相关。
新出现的数据表明，通过抑制SGLT2，糖尿病患者无论有无肾功能损害，肾功能似乎都能得到保留。此外，抑制SGLT2可防止这些患者肾功能进一步恶化和肾病死亡。
