Semaglutide Reduces Heart Failure and Cardiovascular Death in Diabetes With Kidney Disease

What the researchers found

Semaglutide reduced the composite outcome of heart failure events or cardiovascular death (HR 0.73, meaning a 27% reduction, p = 0.0005). When broken down, it reduced heart failure events alone by 27% (HR 0.73, p = 0.0068) and cardiovascular death alone by 29% (HR 0.71, p = 0.0036).

About 19% of participants had heart failure at baseline. The benefit was consistent in both groups: those with pre-existing heart failure (HR 0.73, p = 0.034) and those without (HR 0.72, p = 0.003). Patients with more severe heart failure (NYHA class III) and reduced ejection fraction had higher overall event rates regardless of treatment.

Why it matters

People with both type 2 diabetes and chronic kidney disease have extremely high rates of heart failure and cardiovascular death. This is one of the highest-risk populations in medicine. Showing that semaglutide reduces heart failure events in this group is significant because treatment options for this population are limited and outcomes are poor.

The numbers in context

- 3,533 participants randomized

- Median follow-up: 3.4 years

- HF events or CV death: HR 0.73 (95% CI 0.62-0.87, p = 0.0005)

- HF events alone: HR 0.73 (95% CI 0.58-0.92, p = 0.0068)

- CV death alone: HR 0.71 (95% CI 0.56-0.89, p = 0.0036)

- ~19% had heart failure at baseline

- Primary kidney outcome: 24% reduction (previously reported)

How the study worked

This was a prespecified analysis from the FLOW trial, a randomized, double-blind, placebo-controlled trial. 3,533 participants with type 2 diabetes and chronic kidney disease were randomized 1:1 to weekly subcutaneous semaglutide 1 mg or placebo. The primary trial had already shown a 24% reduction in the main kidney composite outcome. Median follow-up was 3.4 years. Heart failure events and cardiovascular death were adjudicated by an independent committee.

Who was studied

3,533 adults with type 2 diabetes and chronic kidney disease, randomized to semaglutide 1 mg weekly or placebo

What this study cannot tell us

This was a prespecified secondary analysis, not the primary endpoint of the FLOW trial. Heart failure data was collected by investigators, not through a central core lab. The population was specific (T2D plus CKD), so results may not apply to people with heart failure but without kidney disease. The NYHA class III and HFrEF subgroups had too few patients for definitive subgroup conclusions.

How to read the evidence

Rated strong: prespecified analysis from a large, randomized, double-blind, placebo-controlled trial with 3.4 years of follow-up and adjudicated outcomes.

When this study was published

Published in 2024 from the FLOW trial. This is current, high-quality evidence from one of the landmark GLP-1 trials.

The bigger picture

People with both diabetes and kidney disease have among the highest cardiovascular event rates in medicine. Adding heart failure protection to semaglutide's known kidney benefits makes a compelling case for this drug in this high-risk population.

Questions still open

• Does the heart benefit come from weight loss, metabolic improvement, or direct cardiac effects?
• Would these results apply to patients without kidney disease?

Common questions

Read the original research

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.

Journal of the American College of Cardiology, 84(17), 1615-1628

Citation

Pratley, Richard E; Tuttle, Katherine R; Rossing, Peter; Rasmussen, Søren; Perkovic, Vlado; Nielsen, Olav Wendelboe; Mann, Johannes F E; MacIsaac, Richard J; Kosiborod, Mikhail N; Kamenov, Zdravko; Idorn, Thomas; Hansen, Marco Bo; Hadjadj, Samy; Bakris, George; Baeres, Florian M M; Mahaffey, Kenneth W. (2024). Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.. Journal of the American College of Cardiology, 84(17), 1615-1628. https://doi.org/10.1016/j.jacc.2024.08.004