A once-weekly injection of semaglutide significantly reduced the risk of major kidney disease events and cardiovascular outcomes in patients with type 2 diabetes and chronic kidney disease, according to findings from the landmark FLOW trial presented at the American Diabetes Association’s 84th Scientific Sessions in Orlando, Florida and simultaneously published in Nature Medicine.
The double-blind, randomized, placebo-controlled international trial enrolled 3,533 participants, with a median follow-up period of 3.4 years. Researchers compared 1.0 mg of injectable semaglutide weekly with a placebo, administered alongside standard care, to prevent major kidney outcomes – specifically kidney failure, substantial loss of kidney function, and death from kidney or cardiovascular causes.
Participants receiving semaglutide experienced a 24% reduction in the composite primary endpoint, encompassing kidney outcomes and death due to cardiovascular and kidney causes, compared to those receiving a placebo. The study, funded by Novo Nordisk, was halted early at a prespecified interim analysis due to the clear benefits observed in the semaglutide group.
The trial focused on individuals with type 2 diabetes and chronic kidney disease, defined by an estimated glomerular filtration rate (eGFR) of 50 to 75 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio greater than 300 and less than 5000, or an eGFR of 25 to less than 50 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio greater than 100 and less than 5000.
Analysis revealed a 24% lower risk of a primary-outcome event in the semaglutide group (331 events versus 410 in the placebo group; hazard ratio, 0.76; 95% confidence interval, 0.66 to 0.88; P = 0.0003). Similar results were observed for a composite of kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89).
Diabetic kidney disease is a leading cause of end-stage kidney disease globally, with its prevalence mirroring the worldwide diabetes epidemic. The condition likewise carries a markedly increased risk of cardiovascular morbidity and mortality. The FLOW trial represents the first dedicated kidney outcomes trial with a glucagon-like peptide-1 (GLP-1) receptor agonist.
Data presented alongside the FLOW trial results also highlighted the potential benefits of combined therapy with SGLT2 inhibitors, suggesting a synergistic effect in mitigating kidney and cardiovascular risks.
Novo Nordisk has not yet commented on plans for expanded access or pricing adjustments following the publication of the FLOW trial results.
