Once-Weekly Semaglutide Cuts Heart Failure Risk in Diabetes and Kidney Disease: FLOW Trial Analysis

The trial, which involved a high-risk population, has provided crucial insights into how semaglutide can positively impact heart health among individuals already managing these chronic conditions. The findings were published online in the Journal of the American College of Cardiology.

"Semaglutide significantly decreased the time to the first occurrence of composite outcomes related to HF events or CV death, as well as reducing HF events and CV death on their own, in a high-risk population with T2D and CKD. These benefits were observed consistently, regardless of whether patients had a prior history of heart failure," the researchers wrote.

Individuals with type 2 diabetes and CKD face a heightened risk of heart failure (HF) and early mortality due to CV issues. The FLOW study, designed to evaluate the effects of semaglutide—a glucagon-like peptide-1 receptor agonist—on participants with T2D and CKD, found that semaglutide reduced the occurrence of the primary composite outcome (which includes a persistent decline in estimated glomerular filtration rate, advanced kidney failure, kidney replacement therapy, and CV death) by 24%. In light of these findings, Richard E. Pratley, AdventHealth Translational Research Institute, Orlando, Florida, USA, and colleagues conducted a prespecified analysis to assess the impact of semaglutide on heart failure outcomes within this high-risk group.

For this purpose, participants were randomly assigned (1:1) to receive either once-weekly subcutaneous semaglutide at a dose of 1 mg or a placebo. The primary outcome, as outlined in the study, was a composite of heart failure (HF) events, which included new onset or worsening HF resulting in unscheduled hospital admissions or urgent visits, alongside the initiation or intensification of diuretic or vasoactive therapy. The research team collected data on heart failure incidents, while an independent adjudication committee assessed cases of cardiovascular death.

The following were the key findings of the study:

• A total of 3,533 participants were randomized and followed for a median period of 3.4 years.
• At baseline, heart failure was present in 19.4% of participants in the semaglutide group and 19.0% in the placebo group.
• Across the entire trial population, semaglutide was associated with an increased time to the first occurrence of HF events or CV death, showing a hazard ratio (HR) of 0.73.
• It also significantly reduced the incidence of HF events alone (HR: 0.73) and CV death alone (HR: 0.71).
• The risk reduction for the composite HF outcome was consistent in participants with (HR: 0.73) and without (HR: 0.72) a history of HF at baseline.
• Participants classified as NYHA functional class III and those with heart failure with reduced ejection fraction exhibited generally higher risks of HF outcomes (HF events or CV death), regardless of the treatment administered.

This analysis from the FLOW trial showed that once-weekly subcutaneous semaglutide 1.0 mg significantly lowered the risk of heart failure events or cardiovascular death by 27% in a high-risk group with type 2 diabetes and CKD. It also reduced the risk of CV death alone by 29%.

"The benefits of semaglutide were consistent among participants, regardless of whether they had HF at baseline, across various clinical subgroups during a mean follow-up of 3.4 years," the researchers wrote.

Reference:

Pratley RE, Tuttle KR, Rossing P, Rasmussen S, Perkovic V, Nielsen OW, Mann JFE, MacIsaac RJ, Kosiborod MN, Kamenov Z, Idorn T, Hansen MB, Hadjadj S, Bakris G, Baeres FMM, Mahaffey KW; FLOW Trial Committees and Investigators. Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial. J Am Coll Cardiol. 2024 Oct 22;84(17):1615-1628. doi: 10.1016/j.jacc.2024.08.004. Epub 2024 Aug 30. PMID: 39217553.