FLOW Trial Subanalysis: Effect of Semaglutide on Mortality Outcomes

During a late-breaking oral session at ASN Kidney Week 2024, Richard E. Pratley, MD, presented results of a subanalysis of data from the FLOW trial. The trial was designed to assess the effect of semaglutide versus placebo on the progression of renal impairment in people with type 2 diabetes and chronic kidney disease (NCT03819153). The session was titled Effect of Semaglutide on Mortality Outcomes in the FLOW Trial.

Eligible adults ≥18 years were randomized 1:1 to receive either once-weekly subcutaneous semaglutide 1.0 mg or placebo. Study results demonstrated an association between a reduction in the risk of major kidney and cardiovascular events and treatment with semaglutide. For the current analysis of the effect of semaglutide on mortality outcomes, cause of death was confirmed by an event adjudication committee.

Compared to those in the placebo group, the risk of all-cause mortality was reduced among those in the semaglutide group (HR, 0.80; 95% CI, 0.67-0.95). There were also reductions in the risk of cardiovascular death (HR, 0.71; 95% CI, 0.56-0.89) and death of undetermined cause (HR, 0.62; 95% CI, 0.42-0.91) in the semaglutide group compared to the placebo group.

The most common causes of cardiovascular death were sudden cardiac death (2.8% in the semaglutide group vs 3.8% in the placebo group) and heart failure (0.3% in the semaglutide group vs 0.7% in the placebo group). There was no effect of semaglutide on noncardiovascular death or nonkidney-related death. Infection (3.3% in the semaglutide group vs 3.7% in the placebo group) and malignancy (1.4% in the semaglutide group vs 1.2% in the placebo group) were the most common causes of noncardiovascular and nonkidney-related death.

In summary, the researchers said, “In FLOW, semaglutide reduced the risk of all-cause and cardiovascular death by 20% and 29%, and death of undetermined cause by 38%, relative to placebo.”

Source: Pratley RE, Mahaffey KW, Mann J, et al. Effect of semaglutide on mortality outcomes in the FLOW trial. FR-OR109. Abstract of an oral presentation at the American Society of Nephrology Kidney Week 2024; October 25, 2024; San Diego, California. Funding for the study was provided by Novo Nordisk.