Trial Investigates Weight Loss Drug for Patients with Heart Failure

It is widely acknowledged that adopting a healthier lifestyle and losing weight can improve the outlook for individuals with medical conditions. With this in mind, can a weight loss drug be beneficial for people with heart failure? The answer may be yes, according to the findings of a recent clinical trial of semaglutide, a glucagon-like peptide-1 (GLP-1) analog drug, in patients with obesity and heart failure with preserved ejection fraction (HFpEF). The trial was published in the New England Journal of Medicine.

Heart failure is a chronic condition in which the heart progressively loses the ability to pump blood. Symptoms crop up as fatigue, shortness of breath, weakness, swollen legs and feet, and reduced ability to walk or perform daily activities. In the United States, approximately 3 million people have HFpEF, a specific type of symptomatic heart failure in which the heart muscle is stiffened but retains a close-to-normal ejection fraction. This refers to the amount of blood pumped out of the left ventricle with each heartbeat.

Obesity is a well-known risk factor for HFpEF, and people with this dual diagnosis face an increased risk of adverse cardiovascular events. Currently, no treatments have been specifically approved for obesity-related HFpEF. Considering that less than half of those diagnosed with heart failure live beyond five years, better treatment options are urgently needed.

In the present study, the STEP-HFpEF trial investigators aimed to evaluate the effectiveness of semaglutide in improving cardiac function and reducing cardiovascular events. The trial's primary outcome was a composite of cardiovascular death, hospitalization for heart failure, or emergency presentation for heart failure.

In this 52-week study, patients with HFpEF and obesity who injected semaglutide 2.4 milligrams once weekly experienced better results — they reported fewer symptoms, felt less physically limited, lost more weight, and could walk longer in a 6-minute test — compared with patients who took a placebo. Semaglutide also reduced C-reactive protein (CRP), a marker of inflammation, more effectively than the placebo.

Semaglutide, originally developed as a treatment for type 2 diabetes, has shown potential benefits in other cardiovascular conditions. This study adds to the growing body of evidence supporting the potential role of semaglutide in improving outcomes in heart failure patients with obesity.

This and future related research may help resolve the ongoing debate about weight and weight loss in individuals with heart failure. Some previous studies suggested that having a higher body mass index (BMI) might be linked to a better outlook for heart failure patients while losing weight could be associated with a worse outcome, known as “the obesity paradox.”

Regarding this paradox, the authors wrote, “Collectively, these findings support the hypothesis that the range of benefits seen with semaglutide were not simply due to weight loss alone; rather, the pathophysiological processes that underlie heart failure with preserved ejection fraction syndrome itself improved at the same time that weight was lost.”

Semaglutide is not currently indicated for heart failure. However, these findings provide a strong foundation for future trials and new potential indications. Medicare and other payers may benefit from such a development, as it could reduce long-term medical expenses due to fewer hospitalizations and reduced need for related procedures and other treatments.

Novo Nordisk, drug manufacturer of semaglutide (Ozempic, Wegovy), funded the study.