Table1_Disparities in efficacy and safety of sodium-glucose cotransporter 2 inhibitor among patients with different extents of renal dysfunction: A systematic review and meta-analysis of randomized controlled trials.DOCX

Background: The pleiotropic efficacy of SGLT2is in patients with different eGFR levels has not been well-understood. This systematic review and meta-analysis assessed the disparities in the efficacy and safety of SGLT2i treatment across stratified renal function.Methods: We searched four databases from inception to December 2021. We included randomized controlled trials (RCTs) with reported baseline eGFR levels and absolute changes from baseline in at least one of the following outcomes: HbA1c, body weight, blood pressure, and eGFR. Continuous outcomes were evaluated as the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Categorical outcomes were evaluated as odds ratios (ORs) and accompanying 95% CIs.Results: In total, 86 eligible RCTs were included. SGLT2is produces a substantial benefit in glycemic control, weight control, and blood pressure control even in patients with impaired renal function. HbA1c and weight reductions observed in SGLT2i users were generally parallel with the renal function levels, although there was an augmented weight reduction in severe renal dysfunction stratum [HbA1c: −0.49% (−0.58 to −0.39%) for normal renal function, −0.58% (−0.66 to −0.50%) for mild renal function impairment, −0.22% (−0.35 to −0.09%) for moderate renal function impairment, and −0.13% (−0.67 to 0.42%) for severe renal function impairment (p < 0.001 for subgroup differences); weight: −2.12 kg (−2.66 to −1.59 kg) for normal renal function, −2.06 kg (−2.31 to −1.82 kg) for mild renal function impairment; −1.23 kg (−1.59 to −0.86 kg) for moderate renal function impairment; −1.88 kg (−3.04 to −0.72 kg) for severe renal function impairment (p = 0.002 for subgroup differences)]. However, the blood pressure reduction observed in SGLT2i users was independent of renal function. When compared with the placebo, the occurrence of hypoglycemia was more frequent in patients with favorable renal function rather than in those with substantial renal dysfunction.Conclusion: The HbA1c and body weight reductions observed in SGLT2i users were generally parallel with their baseline eGFR levels, while blood pressure reductions in SGLT2i users were independent of their baseline eGFR levels. Consistently, when compared with the placebo, hypoglycemia was more frequent in patients with favorable renal function, where the HbA1c reduction was profound.

背景：SGLT2抑制剂在具有不同估算肾小球滤过率（eGFR）水平患者中的多效性疗效尚未得到充分理解。本研究系统综述和荟萃分析评估了SGLT2抑制剂治疗在分层肾功能中的疗效和安全性差异。方法：我们从起始至2021年12月检索了四个数据库。我们纳入了报告基线eGFR水平和至少一项以下结局的绝对变化（包括HbA1c、体重、血压和eGFR）的随机对照试验（RCTs）。连续性结局以加权平均差异（WMDs）和95%置信区间（CIs）进行评估。分类结局以比值比（ORs）及其伴随的95%置信区间进行评估。结果：总共纳入了86项符合标准的RCTs。SGLT2抑制剂即使在肾功能受损的患者中也能产生显著的血糖控制、体重控制和血压控制益处。SGLT2抑制剂使用者观察到的HbA1c和体重降低通常与肾功能水平平行，尽管在严重肾功能不全组中观察到体重降低更为显著[对于正常肾功能，HbA1c降低为−0.49%（95%置信区间为−0.58%至−0.39%）；对于轻度肾功能损害，HbA1c降低为−0.58%（95%置信区间为−0.66%至−0.50%）；对于中度肾功能损害，HbA1c降低为−0.22%（95%置信区间为−0.35%至−0.09%）；对于严重肾功能损害，HbA1c降低为−0.13%（95%置信区间为−0.67%至0.42%）（亚组差异的p值小于0.001）；体重：对于正常肾功能，体重降低为−2.12公斤（95%置信区间为−2.66公斤至−1.59公斤）；对于轻度肾功能损害，体重降低为−2.06公斤（95%置信区间为−2.31公斤至−1.82公斤）；对于中度肾功能损害，体重降低为−1.23公斤（95%置信区间为−1.59公斤至−0.86公斤）；对于严重肾功能损害，体重降低为−1.88公斤（95%置信区间为−3.04公斤至−0.72公斤）（亚组差异的p值为0.002）。然而，SGLT2抑制剂使用者观察到的血压降低与肾功能无关。与安慰剂相比，在肾功能良好的患者中，低血糖的发生率高于肾功能严重损害的患者。结论：SGLT2抑制剂使用者观察到的HbA1c和体重降低通常与其基线eGFR水平平行，而SGLT2抑制剂使用者的血压降低与其基线eGFR水平无关。一致地，与安慰剂相比，在肾功能良好的患者中，低血糖的发生率更高，其中HbA1c降低更为显著。