Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysis

Abstract Objective This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR < 60 mL/min/1.73 m2, regardless of their diabetic status. Method We...

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Main Authors: Yaru Zhang, Junhui Luo, Bingxin Li, Junying Xu, Hong Yu, Nanlan Chen
Format: Article
Language:English
Published: BMC 2024-11-01
Series:BMC Nephrology
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Online Access:https://doi.org/10.1186/s12882-024-03833-2
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author Yaru Zhang
Junhui Luo
Bingxin Li
Junying Xu
Hong Yu
Nanlan Chen
author_facet Yaru Zhang
Junhui Luo
Bingxin Li
Junying Xu
Hong Yu
Nanlan Chen
author_sort Yaru Zhang
collection DOAJ
description Abstract Objective This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR < 60 mL/min/1.73 m2, regardless of their diabetic status. Method We conducted a full-scale search from MEDLINE, EMBASE and the Cochrane Library database to identify eligible studies up to Jun 2024. All randomized controlled trials (RCTs) comparing cardio-renal outcomes and/or safety of SGLT2i in CKD patients with eGFR < 60 mL/min/1.73 m2 were involved. The relative risk (RR) and 95% confidence interval (CI) for primary outcomes and adverse events were computed by random-effects mode. We used I2 statistic to analyze heterogeneity. Publication bias was assessed by Egger’s test. Results Our study incorporated 17 RCTS, including 27,928 patients. In CKD patients with eGFR < 60 mL/min/1.73 m2, SGLT2i decreased risks of cardiovascular events (seven studies, 17,355 participants, RR 0.77, 95% CI 0.70–0.84), hospitalization for heart failure (HHF) (seven studies, 17,869 participants, RR 0.73, 95% CI 0.65–0.82), cardiovascular death (eight studies, 23,079 participants, RR 0.81, 95% CI 0.74 to 0.88) and renal composite outcomes (eight studies, 22,525 participants, RR 0.70, 95% CI 0.61–0.80) with lower risks of any serious adverse effects(fourteen studies, 19,654 participants, RR 0.91, 95% CI 0.87–0.95), hypoglycemia (nine studies, 16,412 participants, RR 0.91, 95% CI 0.84–0.98), hyperkalemia (four studies, 2693 participants, RR 0.68, 95% CI 0.51–0.93) and acute renal injury (five studies, 5424 participants, RR 0.79, 95% CI 0.65–0.95) compared to placebo. SGLT2i also slowed eGFR decline (total slopes: five studies, 10,370 participants, mean difference 1.17, 95%CI 0.86–1.49; chronic slopes: four studies, 8459 participants, mean difference 2.12, 95%CI 1.64–2.61). Further subgroup analyses revealed that SGLT2i decreased relative risks of cardiovascular outcomes(three studies, 1075 participants, RR 0.76, 95% CI 0.54–0.82), HHF(four studies, 1280 participants, RR 0.74, 95% CI 0.55–1.00) and renal composite outcomes (six studies,4375 participants, RR 0.78, 95% CI 0.68–0.88) with no increased adverse events in the CKD 4 patients. Conclusions SGLT2i significantly improved cardio-renal outcomes and were generally safe in CKD patients with eGFR < 60 mL/min/1.73 m2 and with eGFR < 30 mL/min/1.73 m2. Future large-scale RCTs are needed to confirm the robustness of these results.
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spelling doaj-art-b1ff9810811d4d2facaa010b990125fd2025-08-20T02:18:24ZengBMCBMC Nephrology1471-23692024-11-0125111910.1186/s12882-024-03833-2Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysisYaru Zhang0Junhui Luo1Bingxin Li2Junying Xu3Hong Yu4Nanlan Chen5Department of Nephrology, The Second People’s Hospital of Hunan ProvinceDepartment of Nephrology, The Second People’s Hospital of Hunan ProvinceDepartment of Nephrology, The Second People’s Hospital of Hunan ProvinceDepartment of Nephrology, The Second People’s Hospital of Hunan ProvinceDepartment of Nephrology, The Second People’s Hospital of Hunan ProvinceDepartment of Nephrology, People’s Hospital of Ningxiang City, Ningxiang CityAbstract Objective This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR < 60 mL/min/1.73 m2, regardless of their diabetic status. Method We conducted a full-scale search from MEDLINE, EMBASE and the Cochrane Library database to identify eligible studies up to Jun 2024. All randomized controlled trials (RCTs) comparing cardio-renal outcomes and/or safety of SGLT2i in CKD patients with eGFR < 60 mL/min/1.73 m2 were involved. The relative risk (RR) and 95% confidence interval (CI) for primary outcomes and adverse events were computed by random-effects mode. We used I2 statistic to analyze heterogeneity. Publication bias was assessed by Egger’s test. Results Our study incorporated 17 RCTS, including 27,928 patients. In CKD patients with eGFR < 60 mL/min/1.73 m2, SGLT2i decreased risks of cardiovascular events (seven studies, 17,355 participants, RR 0.77, 95% CI 0.70–0.84), hospitalization for heart failure (HHF) (seven studies, 17,869 participants, RR 0.73, 95% CI 0.65–0.82), cardiovascular death (eight studies, 23,079 participants, RR 0.81, 95% CI 0.74 to 0.88) and renal composite outcomes (eight studies, 22,525 participants, RR 0.70, 95% CI 0.61–0.80) with lower risks of any serious adverse effects(fourteen studies, 19,654 participants, RR 0.91, 95% CI 0.87–0.95), hypoglycemia (nine studies, 16,412 participants, RR 0.91, 95% CI 0.84–0.98), hyperkalemia (four studies, 2693 participants, RR 0.68, 95% CI 0.51–0.93) and acute renal injury (five studies, 5424 participants, RR 0.79, 95% CI 0.65–0.95) compared to placebo. SGLT2i also slowed eGFR decline (total slopes: five studies, 10,370 participants, mean difference 1.17, 95%CI 0.86–1.49; chronic slopes: four studies, 8459 participants, mean difference 2.12, 95%CI 1.64–2.61). Further subgroup analyses revealed that SGLT2i decreased relative risks of cardiovascular outcomes(three studies, 1075 participants, RR 0.76, 95% CI 0.54–0.82), HHF(four studies, 1280 participants, RR 0.74, 95% CI 0.55–1.00) and renal composite outcomes (six studies,4375 participants, RR 0.78, 95% CI 0.68–0.88) with no increased adverse events in the CKD 4 patients. Conclusions SGLT2i significantly improved cardio-renal outcomes and were generally safe in CKD patients with eGFR < 60 mL/min/1.73 m2 and with eGFR < 30 mL/min/1.73 m2. Future large-scale RCTs are needed to confirm the robustness of these results.https://doi.org/10.1186/s12882-024-03833-2Cardiovascular outcomesRenal outcomesSafetySGLT2iChronic kidney diseaseMeta-analysis
spellingShingle Yaru Zhang
Junhui Luo
Bingxin Li
Junying Xu
Hong Yu
Nanlan Chen
Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysis
BMC Nephrology
Cardiovascular outcomes
Renal outcomes
Safety
SGLT2i
Chronic kidney disease
Meta-analysis
title Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysis
title_full Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysis
title_fullStr Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysis
title_full_unstemmed Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysis
title_short Cardio-renal protective effect and safety of sodium-glucose cotransporter 2 inhibitors for chronic kidney disease patients with eGFR < 60 mL/min/1.73 m2: a systematic review and meta-analysis
title_sort cardio renal protective effect and safety of sodium glucose cotransporter 2 inhibitors for chronic kidney disease patients with egfr 60 ml min 1 73 m2 a systematic review and meta analysis
topic Cardiovascular outcomes
Renal outcomes
Safety
SGLT2i
Chronic kidney disease
Meta-analysis
url https://doi.org/10.1186/s12882-024-03833-2
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