Summary: In a prespecified analysis of the double-blind FLOW 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 reduced the composite of first heart failure event or cardiovascular death versus placebo (HR 0.73; 95% CI 0.62-0.87; P=0.0005). The benefit was consistent in participants with and without baseline heart failure.
PICO Summary
| Element | Detail |
|---|---|
| Population | 3,533 adults with type 2 diabetes and chronic kidney disease, randomised 1:1; multicentre, double-blind RCT (FLOW; NCT03819153). Heart failure present at baseline in 19.4% (semaglutide) and 19.0% (placebo); median follow-up 3.4 years. |
| Intervention | Once-weekly subcutaneous semaglutide 1 mg, a GLP-1 receptor agonist (semaglutide arm). |
| Comparison | Once-weekly matched subcutaneous placebo (placebo arm). |
| Outcome | Composite of first HF event 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). Benefit consistent with baseline HF (HR 0.73; 95% CI 0.54-0.98; P=0.0338) and without (HR 0.72; 95% CI 0.58-0.89; P=0.0028). Absolute risk reduction and NNT were not reported in this prespecified analysis. |
FLOW: Semaglutide and Heart Failure Outcomes
RCT · T2D + CKD · median 3.4 yr
In type 2 diabetes with CKD, once-weekly semaglutide cut the composite of heart failure events or cardiovascular death by 27% versus placebo, with consistent benefit whether or not heart failure was present at baseline.
Expert Commentary
This prespecified analysis of the double-blind FLOW trial strengthens the case for semaglutide as a cardiorenal agent rather than a glucose-lowering drug alone. A 27% relative reduction in the composite of heart failure events or cardiovascular death, with directionally concordant signals for each component, was observed in a population at genuinely high risk, and the consistency across those with and without baseline heart failure is reassuring. Several caveats temper enthusiasm. The most important is that heart failure outcomes were a prespecified secondary analysis, not the trial’s primary endpoint, which was a renal and cardiovascular composite reduced by 24%; heart failure events were investigator-reported rather than centrally adjudicated, leaving some room for ascertainment variability, whereas cardiovascular death was adjudicated. The trial was funded by the manufacturer and several authors are company employees, so independent replication remains valuable. Relative effects are reported without absolute risk reduction or number needed to treat, which limits direct bedside translation. Can I use this with my patients? Yes, for adults with type 2 diabetes and chronic kidney disease who fit the FLOW profile, this analysis supports semaglutide where it is tolerated and not contraindicated. Clinicians should weigh cost, gastrointestinal tolerability, and access. Confirmatory adjudicated heart failure data 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