Popular weight-loss drug semaglutide improved heart failure symptoms in a trial of more than 500 people with obesity — providing more evidence that it can improve people’s health in tangible ways, in addition to helping them shed weight.
The challenge: Heart failure is caused by the heart not pumping as much blood as it should. This leads to fatigue, shortness of breath, chest pain, and other symptoms that restrict what people can do and reduce their quality of life.
At least half of all people with heart failure have a kind called “heart failure with preserved ejection fraction” (HFpEF), meaning their heart is able to pump normally, but it doesn’t fill with enough blood.
While being overweight or obese isn’t considered a cause of heart failure, it does increase a person’s risk of developing the condition. The connection is particularly pronounced with HFpEF — in the US, more than 80% of people with that type of heart failure are overweight or obese.
“The benefits … are the largest that we have ever seen with any pharmacologic intervention in this patient population.”
Mikhail Kosiborod
What’s new? A class of drugs called “glucagon-like peptide-1 receptor (GLP-1) agonists,” which were originally developed to treat diabetes, have been making waves in the world of weight loss recently, helping people shed 10-20% of their body weight in several large clinical trials.
Now, researchers have reported that one of the meds — Novo Nordisk’s FDA-approved semaglutide (brand name Wegovy) — reduced heart failure symptoms in a clinical trial involving more than 500 people with HFpEF and obesity.
“The benefits we observed with semaglutide versus placebo on these very important outcomes for patients with this type of heart failure – their symptoms and physical function — are the largest that we have ever seen with any pharmacologic intervention in this patient population,” said Mikhail Kosiborod, the STEP-HFpEF trial’s principal investigator, who presented its findings at the European Society of Cardiology Congress 2023.
The trial: The Novo Nordisk-funded trial included 529 participants with a median body mass index (BMI) of 37 and a median age of 69.
At the start of the trial, they had a median score of 58.9 out of 100 on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a questionnaire commonly used to measure heart failure symptoms (higher scores indicate better health). They could also walk a median distance of 320 meters in 6 minutes.
“These types of improvements can be very impactful for patients living with heart failure.”
Mikhail Kosiborod
For 52 weeks, about half of the trial participants received weekly injections of semaglutide while the others injected a placebo. By the end of the trial, those who received the weight-loss drug dropped an average of 13.3% of their body weight, compared to 2.6% in the placebo group.
The treatment also increased their KCCQ score by an average of 16.6 points and they could walk an average of 21.5 meters farther in six minutes. In the placebo group, KCCQ scores increased by 8.7 points and participants were only able to walk an extra 1.2 meters by the end of the trial.
“We are talking about marked improvements in symptoms such as shortness of breath, fatigue, inability to have physical exertion, swelling,” said Kosiborod. “These types of improvements can be very impactful for patients living with heart failure.”
Why it matters: While the FDA has approved two GLP-1 agonists for weight loss, the drugs cost about $1,000 per month in the US, and insurance often doesn’t cover them, as they’re considered “lifestyle” meds and not medical treatments. Medicare is also prohibited from covering weight-loss drugs.
People who stop taking the drugs typically gain back the weight they’ve lost, too, meaning taking them just long enough to get down to a healthy weight isn’t usually an option.
“We believe that these findings should change the nature of the conversation about the role of obesity in HFpEF.”
Mikhail Kosiborod
Studies like this one, which demonstrate how GLP-1 agonists can improve people’s health — not just help them lower their weight — could encourage more insurance companies to cover the meds. Preliminary results from another study of semaglutide found that the drug cut the risk of heart attacks and strokes by 20%.
“We believe that these findings should also change the nature of the conversation about the role of obesity in HFpEF, as the STEP-HFpEF results clearly indicate that obesity is not simply a comorbidity in patients with HFpEF but a root cause and a target for therapeutic intervention,” said Kosiborod.
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