Heart failure is a known health complication that can occur in people with elevated weight.
As blogged previously, there are two kinds of heart failure:
- Heart failure with reduced ejection fraction (HFrEF) – when the heart is not able to contract properly, after having sustained damage (eg after a heart attack)
- Heart failure with preserved ejection fraction (HFpEF) – when the heart can contract properly, but cannot relax properly, because it has become thick and rigid. This is the type of heart failure that is more closely associated with obesity. In fact, about 80% of people with HFpEF have obesity.
The only medications that have proven to be of benefit in treating HFpEF are the SGLT2 inhibitors (more on this here) – until now.
The STEP HFpEF trial, just published in the New England Journal of Medicine, included 529 people with HFpEF (LFEV ≥45%) and a body mass index (BMI) of 30 or higher, without diabetes, and randomized them to receive either semaglutide 2.4mg weekly (Wegovy) or placebo for one year. The primary endpoints were change from baseline in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, a questionnaire that measures symptoms, physical and social limitations, and quality of life in people with heart failure), and change in body weight.
At one year, the mean change in the KCCQ-CSS was 16.6 points with semaglutide vs 8.7 points with placebo. To put this in perspective, trials of other medications for people with HFpEF such as SGLT2 inhibitors, sacubitril-valsartan, and spironolactone showed changes of only 0.5-2.3 in this score. Weight loss was -13.3% with semaglutide vs -2.6% with placebo. They also found that people in the semaglutide group could walk 20m farther than the placebo group during a 6 minute test, had a greater reduction in inflammation (lower CRP) and NT-proBNP (a blood test marker of heart failure), and a greater number of ‘wins’ (win ratio 1.72 – read more on components of this score in the paper) . Twelve patients in the placebo group had a heart failure event or urgent visit to hospital for heart failure, vs just one in the semaglutide group.
We don’t know how much of the benefit of semaglutide to improve HFpEF was related directly to weight loss vs other mechanisms, like reduction in inflammation and improvement in other metabolic parameters. This study was not powered to analyze hard endpoints (heart failure events), but the imbalance of events in favor of semaglutide is suggestive of benefit.
Semaglutide 2.4mg is also being investigated in people with HFpEF and type 2 diabetes, with about one third of those patients on SGLT2 inhibitors (only 3.6% of patients in the current study were on SGLT2i) ; we look forward to these data as well.
BOTTOM LINE: The benefits of obesity medication semaglutide 2.4mg weekly to improve symptoms of heart failure with preserved ejection fraction (HFpEF) and exercise function while facilitating meaningful weight loss are impressive and important. Whether payors (insurance companies, governments) accept these as sufficient data to pay for treatment remains to be seen.
Disclaimer: I am an investigator in clinical trials of semaglutide. I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide (Novo Nordisk).
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