SELECT Trial Shows Similar Cardiac Benefits of Semaglutide for Heart Failure

Semaglutide (Ozempic, Wegovy; Novo Nordisk) has shown benefits to prevent heart attacks and other major adverse cardiac event (MACE) for those with overweight and cardiovascular disease (CVD), but the benefits of the drug on heart failure (HF) have been unknown. In smaller studies, liraglutide (Victoza), another glucagon-like peptide-1 receptor, showed that the medication could result in harm for those with reduced ejection fraction HF. In a new analysis from the SELECT (NCT03574597) trial, semaglutide showed similar CV benefits for individuals who had heart failure.¹

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“Our previous SELECT analysis showed the benefits of semaglutide for people with cardiovascular disease who had obesity or were overweight. This new study finds that, within this group, people with heart failure did just as well as people without in terms of the outcomes we measured,” John Deanfield, professor at the Institute of Cardiovascular Science at the University College of London, said in a press release.“Our findings show that the benefit of semaglutide was similar regardless of heart failure type.”¹

The initial findings found that weight loss was sustained over 4 years, with a 20% reduction in MACE for adults with a body mass index (BMI) of greater than 27 and pre-existing CVD.²

“More than 55% of semaglutide patients no longer qualified as having obesity BMI of 30+. The dataset adds significantly to the semaglutide evidence—the population had 75% men and most weight loss studies are predominantly in women,” Donna Ryan, MD, professor emeritus at the Pennington Biomedical Research Center, said in an interview.²

In the SELECT trial, there were 17,604 individuals enrolled from 41 countries between October 2018 to March 2021, with 97.1% of those receiving semaglutide and 96.8% on the placebo completing the trial. Approximately 77% of patients met the target dose of 2.4 milligrams subcutaneously weekly by 104 weeks at 2 years. There were 569 CVD events in the semaglutide arm compared with 701 events in the placebo arm.²

In the new analysis, published in The Lancet, investigators found that semaglutide was linked to an approximate 28% reduction in MACE, with events in 9.1% of the semaglutide group and 12.3% in the placebo group. Further, semaglutide resulted in a 24% reduction in CV-related deaths for individuals with pre-existing HF and a 19% reduction of death from any cause. In the previous analysis, there were 223 events of death due to CV events in the semaglutide group and 62 in the placebo group, with Ryan stating that it is not statistically confirmatory that semaglutide is associated with reduction in death from CV-related causes.^1-3

The investigators compared the impact of semaglutide for preserved ejection fraction and reduced ejection fraction, which both have different causes and responses to treatment. The investigators reported that the clinical benefit was seen, regardless of type of HF and was independent of age, sex, BMI, and clinical status.¹

Treatment discontinuation rates were more often seen in the semaglutide group at 14.7% and 9% for the placebo in the HF groups compared with 17.2% and 7.9%, respectively, in the non-HF groups. Serious adverse events were reported more frequently in the placebo group, investigators reported.¹

REFERENCES

1. Weight loss drug’s heart benefits extend to people with heart failure. News release. University College London. August 22, 2024. Accessed August 22, 2024. https://www.eurekalert.org/news-releases/1055249

2. Gallagher A. SELECT Trial: Semaglutide Improves Glycemic Control For Patients at High Risk of Cardiovascular Disease. Pharmacy Times. June 22, 2024. Accessed August 22, 2024. https://www.pharmacytimes.com/view/select-trial-semaglutide-improves-glycemic-control-for-patients-at-high-risk-of-cardiovascular-disease

3. Deanfield J, Verma S, Scirica BM, Kahn SE, et al. Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial. The Lancet. doi:https://doi.org/10.1016/S0140-6736(24)01498-3