Department of Endocrinology and Metabolism, Peking University People's Hospital, No. 11 Xizhimen South Street, Xicheng District, Beijing, 100044, China.
Acta Diabetol. 2023 Mar;60(3):435-445. doi: 10.1007/s00592-022-02022-7. Epub 2023 Jan 7.
To elucidate the association between baseline renal characteristics and the disparities in renal outcomes among patients with SGLT2i treatment.
Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov were searched from inception to November 2022. Event-driven randomized controlled trials of SGLT2i with reports of renal outcomes were included. Sensitivity analyses of prespecified eGFR and UACR subgroups were conducted.
Generally, compared with placebo, the use of SGLT2i was associated with improved renal prognosis (HR = 0.64, 95%CI 0.59-0.70). The magnitude of risk reductions in composite renal outcomes between SGLT2i versus placebo was comparable among different eGFR stratifications (normal renal function: HR = 0.49, 95%CI 0.31-0.79; mild renal impairment: HR = 0.57, 95%CI 0.48-0.68; moderate renal impairment: HR = 0.70, 95%CI 0.63-0.78; severe renal impairment: HR = 0.72, 95%CI 0.62-0.84; P for subgroup difference = 0.09). However, renal benefits seemd to be more prominent in normal to mildly increased albuminuria stratum (HR = 0.51, 95%CI 0.39-0.66) and severely increased albuminuria stratum (HR = 0.57, 95%CI 0.47-0.68), when compared with moderately increased albuminuria stratum (HR = 0.79, 95%CI 0.65-0.96; P for subgroup difference = 0.01).
Generally, the use of SGLT2i was consistently associated with decreased risk of renal events in all prespecified eGFR and albuminuria spectrums, even in patients with substantial renal impairment. The renal benefits of SGLT2i seemed to be independent of baseline eGFR, while the risk reduction in renal events was more profound among patients with mildly increased albuminuria or severely increased albuminuria.
阐明基线肾脏特征与 SGLT2i 治疗患者肾脏结局差异之间的关联。
从建库至 2022 年 11 月,检索了 Pubmed、Medline、Embase、Cochrane 中央对照试验注册库和 Clinicaltrial.gov,纳入了报告肾脏结局的 SGLT2i 事件驱动随机对照试验。对预先设定的 eGFR 和 UACR 亚组进行了敏感性分析。
总体而言,与安慰剂相比,SGLT2i 的使用与改善的肾脏预后相关(HR=0.64,95%CI 0.59-0.70)。在不同 eGFR 分层中,SGLT2i 与安慰剂相比,复合肾脏结局的风险降低幅度相当(肾功能正常:HR=0.49,95%CI 0.31-0.79;轻度肾功能损害:HR=0.57,95%CI 0.48-0.68;中度肾功能损害:HR=0.70,95%CI 0.63-0.78;重度肾功能损害:HR=0.72,95%CI 0.62-0.84;亚组差异的 P 值=0.09)。然而,与中度升高的蛋白尿亚组(HR=0.79,95%CI 0.65-0.96;亚组差异的 P 值=0.01)相比,SGLT2i 的肾脏获益似乎在正常至轻度升高的蛋白尿亚组(HR=0.51,95%CI 0.39-0.66)和重度升高的蛋白尿亚组中更为显著(HR=0.57,95%CI 0.47-0.68)。
总体而言,在所有预先设定的 eGFR 和蛋白尿谱中,SGLT2i 的使用与肾脏事件风险的降低一致相关,即使在肾功能严重受损的患者中也是如此。SGLT2i 的肾脏获益似乎独立于基线 eGFR,而在轻度升高的蛋白尿或重度升高的蛋白尿患者中,肾脏事件的风险降低更为显著。