Semaglutide Winning Streak Continues in CKD With FLOW

In patients with both type 2 diabetes and chronic kidney disease, injectable semaglutide (Ozempic, Novo Nordisk) cuts kidney disease progression, major adverse cardiovascular events, and deaths by 24% compared to placebo, according to topline results from the FLOW trial.

The results, released yesterday, are the latest in a string of clinical-trial wins for the popular GLP-1 receptor agonist and follow close on the heels of the SELECT trial, released last year. SELECT showed that semaglutide significantly reduced rates of hard cardiovascular endpoints compared with placebo in overweight and obese patients with preexisting CVD but without diabetes. FLOW, the double-blind kidney outcomes trial for the agent, was halted on the recommendation of the trials independent data monitoring committee last October after an interim analysis pointed to superior efficacy.

FLOW enrolled 3,533 patients with type 2 diabetes and chronic kidney diseases to injectable semaglutide 1.0 mg or placebo on top of the standard of care, with the aim of preventing progression of kidney disease and cutting CV deaths, as measured by a five-point composite endpoint: onset of persistent ≥ 50% reduction in eGFR compared with baseline, onset of persistent eGFR < 15 mL/min/1.73 m², initiation of chronic kidney replacement therapy (dialysis or kidney transplantation), death from kidney disease or death from cardiovascular disease. Confirmatory secondary endpoints include annual rate of change in eGFR.

In announcing the results this week, the trial sponsor noted that both renal and cardiovascular endpoint reductions contributed to the significant risk reduction with semaglutide. Other “confirmatory secondary endpoints” also supported the add-on medication, a press release notes, and the drug’s safety profile was in line with other semaglutide trials.

“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,” Novo Nordisk Executive Vice President Martin Holst Lange notes in the announcement.

Novo Nordisk expects to file for regulatory approvals of a label expansion for Ozempic in the US and EU in 2024. The detailed results from FLOW will be presented at a scientific conference in 2024.