FLOW Trial: Semaglutide Reduces Risk of Kidney Disease Progression

Treatment with semaglutide significantly reduced the risk of kidney disease-related events in patients with type 2 diabetes and chronic kidney disease (CKD), according to results from the phase FLOW trial.

The randomized, double-blind, parallel-group, placebo-controlled FLOW trial (ClinicalTrials.gov Identifier: NCT03819153) compared the effects of semaglutide 1mg, a glucagon-like peptide-1 (GLP-1) receptor agonist, to placebo as an adjunct to standard of care on kidney outcomes for prevention of progression of renal impairment and risk of renal and cardiovascular (CV) mortality. 

The study enrolled 3533 participants with type 2 diabetes and CKD (defined as estimated glomerular filtration rate [eGFR] ≥50 and ≤75mL/min/1.73 m² and urinary albumin-to-creatinine ratio [UACR] >300 and <5000mg/g or eGFR ≥25 and <50mL/min/1.73m² and UACR >100 and <5000mg/g).

The major efficacy outcome was the time to first occurrence of a composite primary endpoint event, defined as onset of persistent 50% or greater reduction in eGFR according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation compared with baseline, onset of persistent eGFR (CKD-EPI) less than 15 mL/min/1.73 m², initiation of chronic kidney replacement therapy (dialysis or kidney transplantation), and death from kidney disease or death from cardiovascular disease.

Findings showed treatment with semaglutide 1mg reduced the risk of kidney-disease progression as well as cardiovascular and kidney death by 24% compared with placebo. Both the CKD and cardiovascular components of the composite endpoint contributed to the reduction in risk. 

Semaglutide was also found to be superior to placebo for the confirmatory secondary endpoints, which included annual rate of change in eGFR (CKD-EPI), time to occurrence of a major adverse cardiovascular event (nonfatal myocardial infarction, nonfatal stroke, cardiovascular death) and time to occurrence of all-cause death.

“We are very excited about the results from FLOW showing that semaglutide 1mg reduces the risk of kidney disease progression,” said Martin Holst Lange, executive vice president for Development at Novo Nordisk. “Approximately 40% of people with type 2 diabetes have chronic kidney disease, so the positive results from FLOW demonstrate the potential for semaglutide to become the first GLP-1 treatment option for people living with type 2 diabetes and chronic kidney disease.”

According to the Company, additional findings from the trial will be presented at a scientific meeting this year. Results from FLOW will be submitted for regulatory approval of a label expansion for Ozempic^® (semaglutide) in 2024.