Semaglutide reduces HF outcomes in patients with T2D and CKD

This summary is based on the presentation of Richard Pratley, MD (Orlando, FL, US) at the ESC Congress 2024 - Effects of the GLP-1 receptor agonist, semaglutide, on heart failure outcomes: a pre-specified analysis of the FLOW trial in participants with type 2 diabetes and chronic kidney disease.

Introduction and methods

People with T2D and CKD have a high risk of kidney failure and CV outcomes. In the FLOW trial, treatment with semaglutide reduced the composite outcome of kidney events or CV mortality in people with T2D and CKD compared with placebo. In this prespecified analysis of FLOW, the effects of semaglutide versus placebo on HF events were evaluated in patients with T2D and CKD.

The FLOW trial was a multinational, randomized controlled clinical trial in which 3533 adults with T2D and CKD were randomized in a 1:1 ratio to once-weekly semaglutide 1 mg or to placebo on top of standard care. FLOW was an event-driven trial and was stopped early after meeting efficacy criteria. Median follow-up was 3.4 years.

The main HF outcome was a composite of time to first occurrence of HF events, defined as new onset or worsening HF leading to hospitalization for HF or urgent visit, or cardiovascular mortality.

Main results

HF status at baseline

• In FLOW, 19.2% of patients (678 of 3532) had a prior history of HF at baseline.
• Of these participants with a prior history of HF, 47.9% had HFpEF and 18.1% had HFrEF, whereas the HF type was unknown in 33.9% of the participants. Most patients were classified in NYHA functional class II (57.4%), 31.9% in NYHA functional class I, and 10.6% in NYHA functional class III.

Main outcomes

• At 48 weeks, the main HF outcome occurred in 12.6% of patients in the semaglutide group and 16.5% of patients in the placebo group (HR: 0.73; 95%CI: 0.62-0.87; P=0.0005).
• Semaglutide versus placebo reduced both HF events alone (HR: 0.73; 95%CI: 0.58-0.92; P=0.0068) and cardiovascular mortality alone (HR: 0.71; 95%CI: 0.56-0.89; P=0.0036).
• The effects of semaglutide on the main composite endpoint and HF events alone were consistent in patients with and without HF at baseline (P for interaction>0.05).
• Consistent effects on the main HF outcome were seen across all pre-specified subgroups, and were independent of loop diuretics use, MRA use, SGLT2i use, HF subgroups, prior ASCVD and NYHA class.

Conclusion

In this prespecified analysis of FLOW, semaglutide reduced the composite of HF events or cardiovascular mortality in patients with T2D and CKD compared with placebo, regardless of baseline history of HF. A consistent effect was observed across prespecified clinically relevant subgroups.

- Our reporting is based on the information provided at the ESC Congress 2024 -

The findings of this study were simultaneously published in JACC.