Semaglutide Reduces Heart Failure and Cardiovascular Death in Diabetes With Kidney Disease
In the FLOW trial, semaglutide cut heart failure events by 27% and cardiovascular death by 29% in people with type 2 diabetes and chronic kidney disease.
Quick Facts
What This Study 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.
Key Numbers
- 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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't 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.
Questions This Raises
- ?Does the heart benefit come from weight loss, metabolic improvement, or direct cardiac effects?
- ?Would these results apply to patients without kidney disease?
Trust & Context
- Key Stat:
- HR 0.71 for CV death Semaglutide reduced the risk of dying from cardiovascular causes by 29% in this high-risk population
- Evidence Grade:
- Rated strong: prespecified analysis from a large, randomized, double-blind, placebo-controlled trial with 3.4 years of follow-up and adjudicated outcomes.
- Study Age:
- Published in 2024 from the FLOW trial. This is current, high-quality evidence from one of the landmark GLP-1 trials.
- Original Title:
- Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.
- Published In:
- Journal of the American College of Cardiology, 84(17), 1615-1628 (2024)
- Authors:
- Pratley, Richard E(4), Tuttle, Katherine R(10), Rossing, Peter(6), 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
- Database ID:
- RPEP-09089
Evidence Hierarchy
Frequently Asked Questions
Does semaglutide protect the heart in kidney disease?
Yes — the FLOW trial showed a 27% reduction in heart failure events and 29% reduction in cardiovascular death in patients with diabetes and kidney disease.
Do you need to already have heart failure to benefit?
No — the benefit was consistent whether or not patients had heart failure at the start of the study.
Read More on RethinkPeptides
Cite This Study
https://rethinkpeptides.com/research/RPEP-09089APA
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
MLA
Pratley, Richard E, et al. "Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.." Journal of the American College of Cardiology, 2024. https://doi.org/10.1016/j.jacc.2024.08.004
RethinkPeptides
RethinkPeptides Research Database. "Effects of Semaglutide on Heart Failure Outcomes in Diabetes..." RPEP-09089. Retrieved from https://rethinkpeptides.com/research/pratley-2024-effects-of-semaglutide-on
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.