Summary: In a prespecified analysis of the FLOW randomised trial (n=3,533 adults with type 2 diabetes and chronic kidney disease), once-weekly subcutaneous semaglutide 1 mg reduced the composite of heart failure events or cardiovascular death by 27 percent versus placebo (HR 0.73; 95% CI 0.62-0.87; P=0.0005) over a median of 3.4 years. The benefit was consistent in those with and without heart failure at baseline.
PICO Summary
| Element | Detail |
|---|---|
| Population | 3,533 adults with type 2 diabetes and chronic kidney disease at high cardiovascular risk; international multicentre double-blind RCT (FLOW; NCT03819153). Heart failure was present at baseline in 678 participants (19.4% semaglutide, 19.0% placebo). |
| Intervention | Once-weekly subcutaneous semaglutide 1 mg; n=1,767. Median follow-up 3.4 years. |
| Comparison | Matching once-weekly placebo injection (1:1 randomisation); n=1,766. |
| 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 was consistent with (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) baseline heart failure. Absolute risk reduction and number needed to treat were not reported for these outcomes. |
FLOW: Semaglutide and Heart Failure Outcomes
RCT · T2D + CKD · median 3.4 years
Once-weekly semaglutide 1 mg cut the composite of heart failure events or cardiovascular death by 27% versus placebo in type 2 diabetes with chronic kidney disease, consistent regardless of baseline heart failure.
Expert Commentary
This prespecified analysis of the FLOW trial provides reasonably persuasive evidence that once-weekly semaglutide 1 mg lowers heart failure events and cardiovascular death in adults with type 2 diabetes and chronic kidney disease, a population in which heart failure is common and prognostically heavy. The randomised double-blind design, the consistency of the hazard ratio across baseline heart failure status, and the concordant signal for cardiovascular death (independently adjudicated) all strengthen confidence in the finding. The verdict is that the heart failure benefit is real and clinically meaningful, though it should be read as a secondary, hypothesis-supporting result rather than a primary heart failure endpoint. One limitation deserves weight: heart failure events were reported by site investigators rather than centrally adjudicated, which can introduce ascertainment variability, and absolute risk reductions were not provided, so the magnitude of patient-level benefit is harder to anchor. The trial was funded by the manufacturer of semaglutide, and several authors were company employees, which warrants the usual interpretive caution even within a rigorous protocol. 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 adds heart failure and cardiovascular mortality reduction to the existing renal rationale for semaglutide. Clinicians should fold these data into shared decisions while awaiting centrally adjudicated heart failure confirmation.
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