Semaglutide shown to improve cardiovascular outcomes among patients with type 2 diabetes with any forms of heart failure

Abstract

Previous studies have shown the efficacy and effectiveness of semaglutide to help to reduce major adverse cardiac events (MACE) such as heart attacks and strokes for people with obesity or who were overweight and had cardiovascular disease.¹ Whether the benefit persists specifically in patients with heart failure at baseline is unclear. This is important since a diagnosis of heart failure is associated with adverse cardiovascular outcomes.

A new study published in The Lancet, have now found similar cardiovascular benefits for a subgroup of study participants who were determined to have heart failure at the start of the trial.²

The study investigated data from 4286 people—out of a total of 17 605 from the landmark Semaglutide and Cardiovascular Outcomes (SELECT) trial who were randomly assigned either semaglutide or a placebo. Patients were followed up over an average of more than 3 years.

Their analysis found that semaglutide was associated with a 28% reduction in major adverse cardiac events (12.3% in the placebo group compared to 9.1% in the semaglutide group). Among people with pre-existing heart failure, there was a 24% reduction in cardiovascular disease-related deaths and a 19% reduction in deaths of any cause. In addition, the study found the clinical benefit of semaglutide was observed irrespective of type of heart failure (i.e., heart failure with sreduced and preserved ejection fraction). It was also found to be independent of age, sex, baseline BMI, and clinical status. Serious adverse events were reported more frequently in the placebo group than in the semaglutide group. Treatment was discontinued more often in the semaglutide group, primarily driven by the well recognized gastrointestinal disorders (14.7% vs. 9.0% in the heart failure groups; and 17.2% vs. 7.9% in non-heart failure groups).

This study therefore extends the observation from the previously published SELECT which showed benefits of semaglutide for people with cardiovascular disease who had obesity or were overweight. This new study reports that among similar patient group with obesity or overweight, people with heart failure did as well as people without heart failure in reducing major adverse cardiovascular events, cardiovascular related death or any cause of mortality. This is important as there were some uncertainties regarding the safety of Liraglutide, another Glucagon like peptide-1 analogue in people with heart failure with reduced ejection fraction.³

So where does evidence from this study sit in our current strategy to manage heart failure in people with type 2 diabetes? It is important to note that Semaglutide is not licenced for the management of heart failure. Conversely, evidence based from the sodium glucose co-transporter 2 inhibitor suggest clear benefit for patients with heart failure, irrespective of disease status or whether heart failure is associated with preserved or reduced ejection fraction. In addition, the exact mechanism for the benefits of Semaglutide to improve cardiovascular benefits in people with heart failure remains unclear. Nonetheless, the observation that semaglutide reduced all cause mortality in all heart failure groups suggest some pleotropic effects of Semaglutide to improve heart failure outcome, including by reducing adiposity, which is an important risk factor for heart failure progression. A noted limitation with this study is that the majority of study participants were male and a high proportion were white, which limits the ability to generalize treatment outcome.

While this study support the use of semaglutide on top of usual care to reduce risk of major adverse cardiovascular events, further study is first required to evaluate the effects of semaglutide on heart failure-related outcomes. These data is available for the SGLT2 inhibitors. As SELECT was not a dedicated heart failure trial, the study results cannot be extrapolated to patients with heart failure in general. Until then, SGLT2 inhibitor should remain the first treatment option for people with type 2 diabetes with heart failure.