BMC cardiovascular disorders · 2026
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.
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Bao Ziyang, Hu Jingjia, Sun Yue, Li Xianfa, Lin Riyang, Zhu Caifeng, Yin Jiazhen
Аннотация
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.
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.