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Background <p>Elderly patients with non-dialysis chronic kidney disease have high cardiorenal risk. SGLT2 inhibitors are considered to potentially provide combined renal and cardiac benefits.</p> Objective <p>To evaluate renal and cardiovascular outcomes and safety of SGLT2 inhibitors in patients aged ≥ 65 years with non-dialysis chronic kidney disease.</p> Methods <p>Randomized controlled trials from database inception to 2025-7-18 were systematically searched, and trials enrolling non-dialysis chronic kidney disease and reporting a ≥ 65-year subgroup were included. The primary outcome was an adverse renal composite endpoint, and the key secondary outcome was a composite of cardiovascular death or heart failure hospitalization. Safety focused on genital mycotic infections and volume depletion/hypotension, and acute kidney injury (AKI) and diabetic ketoacidosis (DKA) were summarized descriptively. Random-effects models based on log HR or RR (REML, Hartung–Knapp) were used, pre-specified sensitivity analyses were performed, and the certainty of evidence was assessed using GRADE.</p> Results <p>Three double-blind trials including 5,831 patients aged ≥ 65 years were included. SGLT2 inhibitors reduced the risk of the adverse renal composite endpoint (HR = 0.68, 95% CI 0.52–0.89; I²=29.98%), and the risk of the composite of cardiovascular death or heart failure hospitalization (HR = 0.74, 95% CI 0.64–0.86; I²=35.53%). For safety, the risk of genital mycotic infections was increased (RR = 2.40, 95% CI 1.96–2.94; I²=23.85%), and the risk of volume depletion/hypotension was also increased (RR = 1.28, 95% CI 1.09–1.50; I²=0.00%); no signal of increased AKI was observed; DKA was very rare. GRADE rated the certainty of evidence as high for the renal outcome and moderate for the heart failure-related outcome.</p> Conclusion <p>In patients aged ≥ 65 years with non-dialysis chronic kidney disease, SGLT2 inhibitors added to standard therapy achieve dual renal and cardiovascular benefits with a manageable safety profile, supporting their structured use with stratified monitoring. It is recommended that SGLT2 inhibitors be routinely included in treatment.</p>

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Renal and cardiovascular outcomes and safety of SGLT2 inhibitors in patients aged ≥ 65 years with non-dialysis chronic kidney disease: a systematic review and meta-analysis of subgroup-level estimates derived from randomized trials

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月9日

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  • Ziyang Bao,
  • Jingjia Hu,
  • Yue Sun,
  • Xianfa Li,
  • Riyang Lin,
  • Caifeng Zhu,
  • Jiazhen Yin

摘要

Background

Elderly patients with non-dialysis chronic kidney disease have high cardiorenal risk. SGLT2 inhibitors are considered to potentially provide combined renal and cardiac benefits.

Objective

To evaluate renal and cardiovascular outcomes and safety of SGLT2 inhibitors in patients aged ≥ 65 years with non-dialysis chronic kidney disease.

Methods

Randomized controlled trials from database inception to 2025-7-18 were systematically searched, and trials enrolling non-dialysis chronic kidney disease and reporting a ≥ 65-year subgroup were included. The primary outcome was an adverse renal composite endpoint, and the key secondary outcome was a composite of cardiovascular death or heart failure hospitalization. Safety focused on genital mycotic infections and volume depletion/hypotension, and acute kidney injury (AKI) and diabetic ketoacidosis (DKA) were summarized descriptively. Random-effects models based on log HR or RR (REML, Hartung–Knapp) were used, pre-specified sensitivity analyses were performed, and the certainty of evidence was assessed using GRADE.

Results

Three double-blind trials including 5,831 patients aged ≥ 65 years were included. SGLT2 inhibitors reduced the risk of the adverse renal composite endpoint (HR = 0.68, 95% CI 0.52–0.89; I²=29.98%), and the risk of the composite of cardiovascular death or heart failure hospitalization (HR = 0.74, 95% CI 0.64–0.86; I²=35.53%). For safety, the risk of genital mycotic infections was increased (RR = 2.40, 95% CI 1.96–2.94; I²=23.85%), and the risk of volume depletion/hypotension was also increased (RR = 1.28, 95% CI 1.09–1.50; I²=0.00%); no signal of increased AKI was observed; DKA was very rare. GRADE rated the certainty of evidence as high for the renal outcome and moderate for the heart failure-related outcome.

Conclusion

In patients aged ≥ 65 years with non-dialysis chronic kidney disease, SGLT2 inhibitors added to standard therapy achieve dual renal and cardiovascular benefits with a manageable safety profile, supporting their structured use with stratified monitoring. It is recommended that SGLT2 inhibitors be routinely included in treatment.