The diabetes and weight loss drug semaglutide significantly reduced symptoms and improved quality of life in people with obesity and the most common form of heart failure in a clinical trial, potentially expanding the already wildly popular drugs use beyond diabetes and weight loss and offering a new treatment option where few are available.
The study of 529 patients, funded by drugmaker Novo Nordisk, found that a 2.4-milligram weekly dose of semaglutide, sold as Wegovy for weight loss, resulted in an improvement of 17 points on a 100-point scale used to assess symptoms of a condition known as heart failure with preserved ejection fraction. In contrast, placebo participants had a 9-point improvement compared to those who received a placebo. The study was published in the New England Journal of Medicine on Friday.
In real terms, that difference means Wegovy helped people with heart failure have less shortness of breath, fatigue, trouble exercising themselves and swelling, along with better exercise function and quality of life, all part of a scale known as the Kansas City Cardiomyopathy Questionnaire clinical summary score, said Dr. Mikhail Kosiborod, cardiologist and vice president for research at Saint Lukes Mid America Heart Institute, Kansas City, Missouri.
This is the largest treatment benefit we've ever seen for that endpoint in this patient population with any drug, said Dr. Kosiborod, CRNA, at the European Society of Cardiology meeting in Amsterdam.
There are 64 million people globally living with heart failure, Novo Nordisk said in a statement. The heart cannot pump enough blood to meet the needs of the body.
The heart pumps normally but is too stiff to fill properly due to preserved ejection fraction. The study also suggests that this type of heart failure is accounting for more than half of all cases in the US and is increasing in prevalence, Kosiborod said.
The author also reported that 80% of patients with this kind of heart failure in the US have obesity or are characterized as overweight. The other goal of the study was weight loss, and the drug did so, too. Those on semaglutide lost about 13% of their body weight, compared to 2.6% for those on placebo.
Until recently, the main treatment options for people with this kind of heart failure were diuretics, sometimes called water pills, Kosiborod said. They increase urination to reduce fluid in the body and can temporarily alleviate symptoms, but they are woefully insufficient.
Another class of drugs known as SGLT 2 inhibitors, also used for type 2 diabetes, have been shown to reduce the risk of heart failure hospitalization, but it is not enough for most people, Kosiborod said. The symptoms improvements are relatively minor.
The study of semaglutide tested exercise function using a metric known as the six-minute walk test. At the end of the study, it revealed, the drug helped participants walk 20 meters longer than people who got a placebo.
There were fewer serious safety events in the drug group than in the placebo group, although more patients stopped taking semaglutide, mainly because of gastrointestinal issues that are common side effects with this class of drugs, known as GLP - 1 receptor agonists.
The study had a limited diversity: 96% of the participants were white.
We as a clinical trial community know that we need to do better in terms of patients who are Black, Hispanic, and other backgrounds that are underrepresented in clinical trials, Kosiborod said.
In another heart failure trial of semaglutide that includes patients with diabetes, the researchers said, the data collected together could provide a better picture of how the drug works for people of different racial and ethnic backgrounds.
The new data builds on other recent results suggesting Wegovy could be prescribed for reasons beyond weight loss. Novo Nordisk announced in August that Wegovy reduced the risk of heart attack, stroke or heart-related death in people with cardiovascular disease and obesity by 20 percent, a result expected to boost use of the medicine even further. The company is still unable to meet demand and has had to limit access to some lower starter doses of the medication so it can meet supply demands for established patients.
Wegovy and its sister drug for type 2 diabetes, Ozempic, and a similar drug from Eli Lilly called Mounjaro, have been revolutionizing the way doctors approach weight loss with medicines after decades of drugs with weak efficacy and dangerous safety issues.
They are also changing the way researchers think about obesity and the results in heart failure contribute to that paradigm shift, said Dr. Kosiborod.
We cannot continue to treat obesity just as something that happens to these patients, he said. It's likely a root cause of the problems and should be treated as such.
He added that the drug may be helping in ways beyond weight loss: through reducing inflammation and congestion, for example.
As a physician taking care of patients, Kosiborod said that the results were extremely gratifying, as what I now can tell them is that we have pretty definitive evidence that if we prescribe this medication, you will feel better and be able to do more, and it going to have a significant impact on your quality of life.