The landmark FLOW trial has demonstrated that semaglutide, a once-weekly GLP-1 receptor agonist, significantly reduces the risk of major kidney disease events by 24% in patients with type 2 diabetes and chronic kidney disease. The findings, presented at the American Diabetes Association's 84th Scientific Sessions and simultaneously published in Nature Medicine, represent the first dedicated kidney outcomes trial with a GLP-1 receptor agonist.
Trial Design and Patient Population
The double-blind, randomized, placebo-controlled international trial enrolled 3,533 participants with a median follow-up period of 3.4 years. The study compared injectable semaglutide (1.0 mg) administered once weekly with placebo as an adjunct to standard care for preventing major kidney outcomes, specifically kidney failure, substantial loss of kidney function, and death from kidney or cardiovascular causes.
The trial addressed a significant unmet medical need, as kidney disease impacts an estimated 37 million Americans, including nearly 15% of the adult population. Diabetes serves as a major risk factor for kidney disease, with approximately one in three American adults with diabetes developing chronic kidney disease.
Primary and Secondary Outcomes
Participants who received semaglutide experienced a 24% risk reduction of the composite primary endpoint, which included kidney outcomes and death due to cardiovascular and kidney causes, compared to those who received placebo. The primary endpoint encompassed kidney failure, substantial loss of kidney function, and death from kidney or cardiovascular causes.
The secondary endpoints demonstrated significant improvements with semaglutide treatment. The estimated glomerular filtration rate (eGFR) slope, which measures kidney function and determines disease stage, showed a slower decline of 1.16 ml/min/1.73m²/year in the semaglutide group. Additionally, semaglutide reduced major cardiovascular events by 18% and decreased the risk of all-cause death by 20%.
Clinical Significance and Expert Perspectives
"This is a patient population at high-risk of severe kidney outcomes. Despite existing treatment options, there is still a clear unmet need for this group," said Richard E. Pratley, MD, Medical Director at the AdventHealth Diabetes Institute Orlando, FL, and co-chair of the FLOW trial. "The findings from the FLOW trial have the potential to change the disease course of these high-risk patients and pave the way for new treatment strategies, offering hope to millions of patients globally."
Professor Vlado Perkovic, Dean of Medicine and Health and Scientia Professor at UNSW Sydney, who presented research at the 61st European Renal Association Congress, emphasized the clinical impact: "The use of semaglutide in people with type 2 diabetes and chronic kidney disease can lower the risk of major kidney outcomes and reduce the risk of cardiovascular events, cardiovascular death and all-cause death. These benefits signify a profound clinical impact saving kidneys, hearts and lives, for patients with type 2 diabetes and chronic kidney disease."
Safety Profile and Future Research
The trial findings included reassuring safety data, further supporting the potential value of semaglutide in this high-risk patient population. The study authors noted that new research will follow in 2024 and 2025, focusing on clinically relevant areas to address the unmet needs of patients with type 2 diabetes and chronic kidney disease.
The research also highlighted the likely benefits of combined therapy with SGLT2 inhibitors, suggesting potential for combination treatment strategies in managing this complex patient population.
Treatment Implications
The FLOW trial results offer great promise in reshaping treatment strategies for individuals at high risk of diabetes-related complications, providing a new avenue for kidney and cardiovascular protection. The findings demonstrate that semaglutide can slow kidney function decline while simultaneously providing cardiovascular benefits and reducing mortality risk in this vulnerable patient population.
