Presenter: Brendon L. Neuen, MBBS, MSc, PhD, The George Institute for Global Health, Sydney, New South Wales, Australia
Impact of glomerular filtration rate and albuminuria on the effects of SGLT2 inhibitors on kidney outcomes. Abstract FR-OR092. Presented November 7, 2025.
Sodium-glucose cotransporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease across a broad range of estimated glomerular filtration rates and albuminuria levels, according to a meta-analysis presented at American Society of Nephrology Kidney Week 2025.
The benefits of SGLT2 inhibitor treatment were apparent across patient groups, including in those with stage 4 chronic kidney disease and minimal or no albuminuria, according to investigator Brenden L. Neuen, MBBS, MSc, who presented findings in a late-breaking research session.
Taken together, these results support the routine use of SGLT2 inhibitors in patients with type 2 diabetes, chronic kidney disease, or heart failure to improve outcomes across a wide range of kidney function, Dr. Neuen reported.
The analysis by Dr. Neuen and colleagues was an inverse-variance weighted meta-analysis of trials conducted within the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium (SMART-C).
The primary objective of this analysis was to assess the benefit of SGLT2 inhibitors in patients with stage 4 chronic kidney disease or little to no albuminuria.
SGLT2 inhibitors clearly reduce the progression of chronic kidney disease broadly among patients with type 2 diabetes, chronic kidney disease, or heart failure. However, whether their impact varies based on estimated glomerular filtration rate or urine albumin-creatinine ratio remains uncertain.
Thus, investigators looked at the SMART-C data set, assessing the impact of SGLT2 inhibitors across a range of estimated glomerular filtration rates and urine albumin-creatinine ratio values. The primary outcome was a composite of kidney failure, reduction in estimated glomerular filtration rate of 50% or greater, or death from kidney-related causes.
The analysis of SMART-C included randomized, double-blind, placebo-controlled trials of SGLT2 inhibitors with indications to reduce chronic kidney disease progression. The investigators confined the analysis to studies that included 500 participants or more in each group and had at least 6 months of follow-up.
Based on those criteria, they identified 10 studies including more than 70,000 participants.
Of that group, more than 2,000 (approximately 3%) experienced chronic kidney disease progression and about 1,000 (approximately 1%) experienced kidney failure.
Treatment with SGLT2 inhibitors reduced chronic kidney disease progression regardless of baseline estimated glomerular filtration rate or urine albumin-creatinine ratio. The hazard ratio for progression was 0.62 (95% confidence interval 0.57–0.68), according to the report.
Treatment with an SGLT2 inhibitor also reduced kidney failure alone, with a hazard ratio of 0.66 (95% confidence interval 0.58–0.75). The magnitude of protection varied depending on estimated glomerular filtration rate and urine albumin-creatinine ratio. However, the overall treatment benefit, based on the slope of the estimated glomerular filtration rate over time, was evident across nearly all subgroups where there were sufficient participants for analysis.
Findings were presented at American Society of Nephrology Kidney Week 2025 and published simultaneously in JAMA.
Taken together, the findings of this large and collaborative meta-analysis show that SGLT2 inhibitors reduced the risk of all kidney outcomes studied, including kidney failure alone, investigators wrote in the JAMA report.
“Importantly, SGLT2 inhibitors lowered the risk of chronic kidney disease progression across the full spectrum of estimated glomerular filtration rate and urine albumin-creatinine ratio” including those with little to no albuminuria, they added.
That latter group represents a clinical challenge, as current guidelines offer weaker recommendations for them, authors said.
“These findings, representing the totality of the large-scale randomized evidence for SGLT2 inhibitors approved for reducing chronic kidney disease progression, provide the clearest support to date for routine use of SGLT2 inhibitors across the full spectrum of chronic kidney disease,” authors said.
That includes patients with stage 4 chronic kidney disease, who are at the highest risk of kidney failure, and those with little to no albuminuria, they added.
Disclosures
Brendon L Neuen, MBBS, MSc, PhD, and co-authors reported non-US government support for this study.
References
Neuen BL, Fletcher RA, Perkovic V, Heerspink HJ. Impact of glomerular filtration rate and albuminuria on the effects of SGLT2 inhibitors on kidney outcomes [abstract]. Presented at: American Society of Nephrology Kidney Week 2025; November 6–9, 2025; Houston, TX.
Neuen BL, Fletcher RA, Anker SD, et al; SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists’ Consortium (SMART-C). SGLT2 inhibitors and kidney outcomes by glomerular filtration rate and albuminuria: a meta-analysis. JAMA. Published online November 7, 2025. doi:10.1001/jama.2025.20834