July 2024
Study finds semaglutide reduces CKD progression and CV death risk in patients with diabetes and CKD
By Rebecca Jenkins
Once weekly treatment with semaglutide reduces the risk of major kidney disease events and death from cardiovascular (CV) causes in patients with type 2 diabetes and chronic kidney disease (CKD), an Australian-led international trial has found.
It was unknown whether semaglutide would mitigate the high risk of kidney failure, CV events and death, in patients with type 2 diabetes and CKD, researchers led by UNSW Sydney, wrote in The New England Journal of Medicine.
Adults with type 2 diabetes were eligible for the industry-sponsored FLOW (Evaluate Renal Function with Semaglutide Once Weekly) trial if they had high-risk kidney disease and were receiving a stable maximal dose of renin-angiotensin system (RAS) inhibitors.
Among the 5581 screened candidates, 3533 met the entry criteria and were randomly assigned to receive 1.0mg subcutaneous semaglutide weekly (1767 participants) or placebo (1766 participants).
Median follow up was 3.4 years, after a prespecified interim analysis found evidence of efficacy and recommended early cessation.
The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an estimated glomerular filtration rate of <15mL/minute/1.73m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or CV causes.
Researchers found the risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs 410 first events).
‘The number of persons who would need to be treated over three years to prevent one primary outcome event was 20,’ the researchers wrote.
Results were similar for a composite of the kidney-specific components and for death from CV causes, they reported.
Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group.
Professor Carol Pollock, Professor of Medicine at The University of Sydney’s Kolling Institute in Sydney, said this was the first trial demonstrating kidney and CV protection from a glucagon-like peptide 1 (GLP-1) receptor agonist.
Professor Pollock, who is also Chair of Kidney Health Australia, said the trial had a robust methodology and all components of the primary endpoint were statistically significant, even though the study was stopped early.
Commenting on a possible mechanism, Professor Pollock said GLP-1 receptor agonists had been shown to reduce inflammatory cell infiltration, the production of inflammatory and fibrotic mediators and oxidative stress in the kidney.
‘Lowering of blood glucose, body weight and a small reduction in systolic blood pressure may also contribute to kidney protection, but it is highly unlikely these factors alone account for the benefit of semaglutide,’ she said.
Professor Pollock said the next questions to be answered related to how kidney protectives should be optimally used: either simultaneously in a ‘pillars’ model or sequentially, with drugs switched out if they were not working.