SGLT2 Inhibitors Reduce CKD Progression Across All Kidney Function Levels: JAMA
Australia: A new meta-analysis has found that SGLT2 inhibitors significantly lower the risk of chronic kidney disease (CKD) progression regardless of baseline estimated glomerular filtration rate (eGFR) or albuminuria levels — including in patients with stage 4 CKD or minimal albuminuria — supporting their broad use to improve kidney outcomes in type 2 diabetes, CKD, and heart failure.
The study, published in JAMA by Brendon L. Neuen and colleagues from The George Institute for Global Health, University of New South Wales, Sydney, analyzed data from 70,361 participants across 10 randomized, placebo-controlled trials. Results showed that SGLT2 inhibitors substantially reduced the risk of CKD progression, kidney failure, and serious acute kidney injury.
The key findings were as follows:
- SGLT2 inhibitors consistently reduced the risk of CKD progression across all eGFR subgroups, lowering overall risk by 38% (HR 0.62).
- The hazard ratios remained similar across eGFR categories — 0.61 (≥60), 0.57 (45–<60), 0.64 (30–<45), and 0.71 (<30) — showing no significant variation by kidney function.
- Benefits were also consistent across albuminuria levels, with hazard ratios of 0.58 (≤30 mg/g), 0.74 (>30–300 mg/g), and 0.57 (>300 mg/g).
- SGLT2 inhibitors slowed the annual decline in eGFR in both diabetic and non-diabetic participants, highlighting a renal-protective effect independent of glycemic control.
- The treatment further reduced the risk of kidney failure alone (HR 0.66).
According to the authors, these results reinforce that the kidney-protective benefits of SGLT2 inhibitors extend beyond diabetic populations and apply to patients across the spectrum of CKD severity and albuminuria. This broad efficacy supports the inclusion of SGLT2 inhibitors as a standard therapeutic option in managing CKD, irrespective of baseline parameters.
The researchers noted a few limitations — data on patients with severely reduced eGFR (<20 mL/min/1.73 m²) came from only one trial (EMPA-KIDNEY), limiting conclusions for this group. Moreover, the small number of events in participants without diabetes or with normal albuminuria reduced statistical power, and variations in trial criteria and populations may affect generalizability.
Despite these limitations, the findings offer compelling evidence for the routine use of SGLT2 inhibitors to prevent CKD progression and kidney failure. The authors emphasized that upcoming trials, such as RENAL LIFECYCLE, will provide further insights into their role in patients with advanced kidney impairment and those on dialysis or with kidney transplants.
"Overall, the comprehensive meta-analysis highlights that SGLT2 inhibitors are effective across a wide range of kidney function and albuminuria levels, marking a significant advancement in the management of CKD and kidney-related outcomes in patients with or without diabetes," the authors concluded.
Reference:
Neuen BL, Fletcher RA, Anker SD, et al. SGLT2 Inhibitors and Kidney Outcomes by Glomerular Filtration Rate and Albuminuria: A Meta-Analysis. JAMA. Published online November 07, 2025. doi:10.1001/jama.2025.20834
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