Liu Geng, Zhong Xueyu, Zheng Juan, Zhang Jiaoyue, Kong Wen, Hu Xiang, Min Jie, Xia Wenfang, Zeng Tianshu, Chen Lulu
Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
Diabetes Ther. 2023 May;14(5):789-822. doi: 10.1007/s13300-023-01391-8. Epub 2023 Mar 13.
Albuminuria, or elevated urinary albumin-to-creatine ratio (UACR), is a biomarker for chronic kidney disease that is routinely monitored in patients with type 2 diabetes (T2D). Head-to-head comparisons of novel antidiabetic drugs on albuminuria outcomes remain limited. This systematic review qualitatively compared the efficacy of novel antidiabetic drugs on improving albuminuria outcomes in patients with T2D.
We searched the MEDLINE database until December 2022 for Phase 3 or 4 randomized, placebo-controlled trials that evaluated the effects of sodium-glucose co-transporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors on changes in UACR and albuminuria categories in patients with T2D.
Among 211 records identified, 27 were included, which reported on 16 trials. SGLT2 inhibitors and GLP-1 RAs decreased UACR by 19-22% and 17-33%, respectively, versus placebo (P < 0.05 for all studies) over median follow-up of ≥ 2 years; DPP-4 inhibitors showed varying effects on UACR. Compared with placebo, SGLT2 inhibitors decreased the risk for albuminuria onset by 16-20% and for albuminuria progression by 27-48% (P < 0.05 for all studies) and promoted albuminuria regression (P < 0.05 for all studies) over median follow-up of ≥ 2 years. Evidence on changes in albuminuria categories with GLP-1 RA or DPP-4 inhibitor treatment were limited with varying outcome definitions across studies and potential drug-specific effects within each class. The effect of novel antidiabetic drugs on UACR or albuminuria outcomes at ≤ 1 year remains poorly studied.
Among the novel antidiabetic drugs, SGLT2 inhibitors consistently improved UACR and albuminuria outcomes in patients with T2D, with continuous treatment showing long-term benefit.
蛋白尿或尿白蛋白与肌酐比值（UACR）升高是慢性肾病的生物标志物，在2型糖尿病（T2D）患者中需定期监测。新型抗糖尿病药物对蛋白尿结局的直接比较仍然有限。本系统评价定性比较了新型抗糖尿病药物对改善T2D患者蛋白尿结局的疗效。
我们检索MEDLINE数据库至2022年12月，查找评估钠-葡萄糖协同转运蛋白2（SGLT2）抑制剂、胰高血糖素样肽-1受体激动剂（GLP-1 RAs）和二肽基肽酶-4（DPP-4）抑制剂对T2D患者UACR变化和蛋白尿分类影响的3期或4期随机、安慰剂对照试验。
在识别出的211条记录中，纳入了27条，涉及16项试验。在≥2年的中位随访期内，与安慰剂相比，SGLT2抑制剂和GLP-1 RAs分别使UACR降低了19%-22%和17%-33%（所有研究P<0.05）；DPP-4抑制剂对UACR的影响各不相同。与安慰剂相比，在≥2年的中位随访期内，SGLT2抑制剂使蛋白尿发生风险降低了16%-20%，蛋白尿进展风险降低了27%-48%（所有研究P<0.05），并促进了蛋白尿的消退（所有研究P<0.05）。关于GLP-1 RA或DPP-4抑制剂治疗后蛋白尿分类变化的证据有限，各研究的结局定义不同，且每类药物内存在潜在的药物特异性效应。新型抗糖尿病药物在≤一年时对UACR或蛋白尿结局的影响仍研究不足。
在新型抗糖尿病药物中，SGLT2抑制剂持续改善T2D患者的UACR和蛋白尿结局，持续治疗显示出长期益处。
