Summary: In a prespecified analysis of the FLOW randomised trial (n=3,533 adults with type 2 diabetes and chronic kidney disease, median follow-up 3.4 years), once-weekly subcutaneous semaglutide 1 mg lowered the risk of the composite of heart failure events or cardiovascular death versus placebo (HR 0.73; 95% CI 0.62-0.87; P=0.0005), with consistent benefit whether or not heart failure was present at baseline.
PICO Summary
| Element | Detail |
|---|---|
| Population | 3,533 adults with type 2 diabetes and chronic kidney disease (heart failure present at baseline in 19.4% semaglutide vs 19.0% placebo); randomised, double-blind, placebo-controlled multicentre prespecified analysis of the FLOW trial (NCT03819153); international. |
| Intervention | Once-weekly subcutaneous semaglutide 1 mg (1:1 randomisation; semaglutide arm). |
| Comparison | Matching once-weekly subcutaneous placebo (1:1 randomisation; placebo arm). |
| Outcome | Composite of heart failure events or cardiovascular death: HR 0.73 (95% CI 0.62-0.87; P=0.0005). Heart failure events alone: HR 0.73 (95% CI 0.58-0.92; P=0.0068). Cardiovascular death alone: HR 0.71 (95% CI 0.56-0.89; P=0.0036). Effect consistent with baseline heart failure (HR 0.73; 95% CI 0.54-0.98; P=0.0338) and without it (HR 0.72; 95% CI 0.58-0.89; P=0.0028). Absolute risk reduction and number needed to treat were not reported in the abstract. |
FLOW: Semaglutide and Heart Failure Outcomes
Prespecified RCT analysis · T2D + CKD · 3.4 yr median
In type 2 diabetes with CKD, once-weekly semaglutide cut the risk of heart failure events or cardiovascular death by 27%, with benefit regardless of baseline heart failure status.
Expert Commentary
This prespecified analysis of the FLOW trial strengthens the case that semaglutide offers cardiovascular protection beyond glycaemia in a population that is notoriously hard to treat. Because heart failure outcomes were a prespecified analysis rather than the primary kidney endpoint, the findings should be read as supportive rather than definitive, yet the randomised, double-blind design and the internal consistency across the composite, its components, and both baseline heart failure strata lend them weight. A hazard ratio of 0.73 for heart failure events or cardiovascular death, with concordant reductions in each component, is clinically meaningful in a group at high absolute risk. The principal limitation worth weighing is that absolute risk reduction and number needed to treat were not provided in the abstract, so the magnitude of patient-level benefit cannot be fully judged from these data alone, and heart failure subtype categorisation relied partly on investigator-reported information. The trial was funded by the manufacturer and several authors are employees of the sponsor, which warrants the usual caution although it does not undermine the randomised comparison. Can I use this with my patients? Yes, for adults with type 2 diabetes and chronic kidney disease who fit the FLOW profile, this supports semaglutide where an agent with cardiorenal benefit is sought. Confirmatory dedicated heart failure endpoints would be welcome.
References
Pratley RE, Tuttle KR, Rossing P, et al. Effects of semaglutide on heart failure outcomes in diabetes and chronic kidney disease in the FLOW trial. J Am Coll Cardiol. 2024;84(17):1615-1628. doi:10.1016/j.jacc.2024.08.004