Landmark Study: SGLT2 Inhibitors Show Broad Benefits for Chronic kidney Disease, Even Without Diabetes
A new meta-analysis of over 70,000 participants provides the strongest evidence yet that SGLT2 inhibitors can substantially slow the progression of chronic kidney disease (CKD) and reduce hospitalizations, regardless of diabetes status or kidney function. The findings, presented at the American Society of Nephrology Kidney Week meeting and published concurrently in JAMA, represent a potential paradigm shift in how CKD is treated globally.
Key Findings Challenge Existing Treatment Paradigms
For years, SGLT2 inhibitors were primarily prescribed to individuals with type 2 diabetes to manage blood sugar. However, growing evidence suggested potential benefits for kidney health, prompting questions whether these benefits extended to individuals without diabetes.This new research decisively addresses those concerns.
Researchers,working through the SGLT2 Inhibitor Meta-analysis Cardio-Renal Trialists’ Consortium (SMART-C) and led by The George Institute for Global Health,found that SGLT2 inhibitors reduced the risk of CKD progression by 38% compared to placebo. Critically, this benefit remained consistent across all levels of kidney function, measured by estimated glomerular filtration rate (eGFR). The annual rate of eGFR decline was also slowed by an impressive 51% with SGLT2 inhibitor use, again demonstrating benefits across the spectrum of kidney function and albuminuria levels.
“These effects were observed even in people with stage 4 CKD (eGFR <30 mL/min/1.73m) and those with minimal or no albuminuria (urine albumin-creatinine ratio, uACR ≤30 mg/g),” explained Associate Professor Brendon Neuen, Renal and Metabolic Programme Lead at The George Institute and lead author of one of the studies. “These are groups for whom SGLT2 inhibitor treatment recommendations have not been clear until now.”
Hospitalizations Significantly Reduced, Safety Profile Confirmed
A second analysis focused on the impact of SGLT2 inhibitors on hospitalizations, revealing substantial benefits for all patients. Hospitalizations due to heart failure were reduced by nearly a third in patients with diabetes and by a quarter in those without the condition. Importantly, the risk of serious adverse events associated with SGLT2 inhibitors remained low and was overwhelmingly outweighed by the positive health outcomes and reduced mortality.
According to a senior official involved in the research, “SGLT2 inhibitors are a powerful tool to reduce the burden of kidney failure, hospitalization, and premature death in patients with diabetes, CKD, or heart failure.” The findings suggest that a significantly larger population than currently treated could benefit from these medications, presenting a major opportunity to improve public health.
Neuen added, “Our findings support simplifying treatment guidelines to encourage broader use of these medicines.”
Global Implications for a Growing Health Crisis
CKD affects approximately 850 million people worldwide – roughly one in ten individuals – and is a leading cause of death and disability. The burden of the disease is particularly acute in low- and middle-income countries,where access to SGLT2 inhibitors is frequently enough limited.
“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,” stated Neuen.
SMART-C is co-chaired by Associate Professor Brendon Neuen and Professor Hiddo heerspink of The George Institute for Global Health.
Source: george Institute for Global Health
Journal references: Neuen, B. L., et al. (2025).SGLT2 Inhibitors and Kidney Outcomes by Glomerular Filtration Rate and Albuminuria. biopsychosocial Science and Medicine. Doi: 10.1001/jama.2025.20834. https://jamanetwork.com/journals/jama/fullarticle/2841163#250650261
