Comprehensive analysis supports routine use of metabolic drug for people with all levels of kidney function

The results of two large-scale studies demonstrate that sodium-glucose co-transporter 2 (SGLT2) inhibitors significantly reduce the risk of kidney disease progression, hospitalisation, and death in people with and without diabetes, regardless of their kidney function.^1,2

In late-breaking presentations at the American Society of Nephrology Kidney Week meeting and simultaneously published in two companion papers in JAMA, the findings are based on data from over 70,000 participants across 10 major randomised controlled trials. The meta-analyses were conducted by the SGLT2 Inhibitor Meta-analysis Cardio-Renal Trialists’ Consortium (SMART-C), led by The George Institute for Global Health.

SGLT2 inhibitors, originally developed to treat type 2 diabetes, have since demonstrated substantial protection against heart failure and chronic kidney disease (CKD).³ However, questions remained about their effectiveness in people with advanced CKD or those with low levels of albuminuria (protein in the urine - a sign of early kidney disease), and whether benefits extended equally to those without diabetes.

In the first analysis, researchers found that SGLT2 inhibitors reduced the risk of CKD progression by 38% versus placebo and were similar across patients regardless of their kidney function (measured by estimated glomerular filtration rate or eGFR. SGLT2 inhibitors slowed the annual rate of eGFR decline by 51% versus placebo, with benefits across all levels of kidney function and rates of albuminuria.

Importantly, these effects were observed even in people with stage 4 CKD (eGFR <30 mL/min/1.73m²) and those with minimal or no albuminuria (urine albumin-creatinine ratio, uACR ≤30 mg/g) – groups for whom SGLT2 inhibitor treatment recommendations have not been clear.

The second analysis focused on the benefits and risks of SGLT2 inhibitors by diabetes status and albuminuria level. It found that substantial benefits were also for all patients, particularly in reducing hospitalisations. Heart failure hospitalisations were reduced by nearly a third in patients with diabetes and a quarter in those without. The risk of serious adverse events was low and considerably outweighed by the health and mortality benefits.

The researchers say the findings provide the strongest evidence yet to support widespread use of SGLT2 inhibitors in people with CKD.

“

SGLT2 inhibitors are a powerful tool to reduce the burden of kidney failure, hospitalisation and premature death in patients with diabetes, CKD, or heart failure. These findings indicate that many more individuals than are currently being treated stand to benefit, highlighting a major opportunity to improve population health. Our findings support simplifying treatment guidelines to encourage broader use of these medicines.

By:

Associate Professor Brendon Neuen

Renal and Metabolic Program Lead at The George Institute

CKD affects around one in ten people globally - approximately 850 million individuals - and is a leading cause of death and disability.4 The burden of CKD is highest in low- and middle-income countries where access to SGLT2 inhibitors remains low.

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As these medicines become more affordable and widely available in generic form over the next few years, we have a once-in-a-generation opportunity to transform care for millions of people living with or at risk of developing kidney disease around the world.

By:

A/Prof Brendon Neuen

SMART-C is co-chaired by A/Prof Brendon Neuen and Professor Hiddo Heerspink of The George Institute for Global Health.

References

1. Neuen BL, et al. SGLT2 inhibitors and kidney outcomes by glomerular filtration rate and albuminuria: A collaborative meta-analysis. JAMA. 2025. https://doi.org/10.1001/jama.2025.20834

2. Staplin N, et al. Absolute effects of sodium glucose co-transporter-2 inhibitors by diabetes status and level of albuminuria: A SMART-C meta-analysis. JAMA. 2025. https://doi.org/10.1001/jama.2025.20835

3. The Nuffield Department of Population Health and the SGLT2 Inhibitor Meta-Analysis Cardio-Renal Trialists' Consortium. Impact of diabetes on the effects of sodium glucose co-transporter-2 inhibitors on kidney outcomes: collaborative meta-analysis of large placebo-controlled trials. Lancet. 2022. https://doi.org/10.1016/S0140-6736(22)02074-8

4. Kovesdy CP, et al. Epidemiology of chronic kidney disease: an update 2022. Kidney Iny Suppl. 2022. https://doi.org/10.1016/j.kisu.2021.11.003