Semaglutide benefits in patients with HFpEF and obesity

By Rebecca Jenkins

In patients with heart failure with preserved ejection fraction (HFpEF) and obesity, once-weekly treatment with semaglutide leads to greater improvements in HF-related symptoms, physical capacity and weight loss than placebo, a study finds.

HFpEF is increasing in prevalence, especially in people with obesity, researchers reported in The New England Journal of Medicine, but there are no approved therapies for obesity-related HFpEF.

In the industry-sponsored trial, 529 patients with HFpEF and a BMI of 30kg/m2 or higher were randomised to receive a once-weekly dose of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide (2.4mg subcutaneously) or placebo for 52 weeks.

Patients were eligible for the trial if they had a left ventricular ejection fraction of at least 45% (most had an ejection fraction of 50%) and no history of diabetes.

At 52 weeks, semaglutide-treated patients saw a mean improvement of 16.6 points in their scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a validated measure of heart failure-related symptoms and physical limitations, compared with an 8.7-point improvement in the placebo group.

Patients in the treatment group saw a 13.3% loss in body weight at one year compared with a 2.6% loss in the placebo group.

In addition, semaglutide increased exercise function compared with placebo, as measured by the 6-minute walk distance, researchers noted.

Associate Professor Clare Arnott, Director of Global Chronic and Complex Diseases and Cardiovascular Programs at the Sydney office of The George Institute for Global Health, said the trial was ‘extremely exciting’ as it was the first large semaglutide study in a dedicated HFpEF population.

‘To date we only have one drug class proven to improve hard clinical endpoints in HFpEF, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, so there is a great need for evidence in this space,’ she told Medicine Today.

‘This is an important, robust and vital study, but must be followed closely by a larger trial in this population powered to look at clinical endpoints such as hospitalisation for heart failure and CV death.’

It is encouraging to see that 56% of participants were women, which is roughly indicative of the sex distribution seen in HFpEF in the community and the authors should be congratulated on this, she said, but it is concerning that 95.8% were White.

‘I also note that very few patients were on an SGLT-2 inhibitor. Future studies will hopefully include a larger proportion of patients on this treatment so we can understand the additive and potentially synergistic benefits of combination therapy,’ she said.

Professor Arnott said HFpEF was a heterogeneous condition with several phenotypes; however, it did appear to have common multisystem, pathophysiological drivers, including inflammation and microvascular disease.

‘Addressing these multisystem issues and concomitant comorbidities, such as obesity, hypertension and atrial fibrillation, that both drive the development of the condition and worsen the prognosis is essential,’ she said.

N Engl J Med 2023; doi: 10.1056/NEJMoa2306963.