Semaglutide eases heart failure symptoms in people with obesity and type 2 diabetes

A year-long trial in people who have obesity-related heart failure with preserved ejection fraction, or HFpEF, and type 2 diabetes found that weekly semaglutide 2.4 mg produced larger improvements in heart failure symptoms, physical limitations and body weight than placebo, according to results published in the New England Journal of Medicine ^[3].

Semaglutide is the molecule in Ozempic, Wegovy and Rybelsus. The 2.4 mg weekly dose studied here is the Wegovy dose approved for long-term weight management ^[1]. Wegovy is not approved to treat heart failure; it is under FDA review for that use ^[2].

The study, called STEP-HFpEF DM, randomly assigned 616 adults who had HFpEF, a body-mass index of 30 or higher, and type 2 diabetes to receive semaglutide or placebo for 52 weeks ^[3].

What the trial measured

Symptoms and physical function were tracked with the Kansas City Cardiomyopathy Questionnaire clinical summary score, a 0-to-100 scale on which higher scores mean fewer symptoms and physical limits ^[1][3]. Scores rose by an average of 13.7 points with semaglutide and 6.4 points with placebo, a difference of 7.3 points (95% confidence interval, 4.1 to 10.4) ^[3].

Body weight fell by an average of 9.8% with semaglutide and 3.4% with placebo, a difference of 6.4 percentage points ^[3]. On a six-minute walk test, the between-group difference was 14.3 meters ^[3]. A combined measure that counted deaths, heart failure events and differences in symptom scores and walking distance favored semaglutide, with a win ratio of 1.58 ^[3]. C-reactive protein, a marker of inflammation, was 33% lower with semaglutide than placebo ^[3].

Serious adverse events were reported in 55 participants (17.7%) in the semaglutide group and 88 (28.8%) in the placebo group ^[3]. The publication does not describe what those events were, and it does not report how many individual participants felt a difference in daily life.

How it compares with the first trial

The earlier STEP-HFpEF trial studied 529 people with HFpEF and obesity but excluded anyone with diabetes ^[1]. In that trial, symptom scores rose 16.6 points with semaglutide versus 8.7 with placebo, weight fell 13.3% versus 2.6%, and six-minute walk distance improved by 21.5 meters versus 1.2 meters ^[1]. The win ratio was 1.72, C-reactive protein fell 43.5% versus 7.3%, and serious adverse events were reported in 13.3% of the semaglutide group and 26.7% of the placebo group ^[1]. The weight loss and some other improvements were somewhat smaller in the diabetes trial than in the earlier one ^[1][3].

Why it matters for patients

HFpEF accounts for more than half of all heart failure cases in the United States, and most people who have it also have overweight or obesity ^[1]. The group studied in STEP-HFpEF DM — obesity, type 2 diabetes and HFpEF together — is common, and the trial's authors note that no approved therapy specifically targets obesity-related HFpEF in people with type 2 diabetes ^[3].

Semaglutide's approved uses depend on the brand: Ozempic and Rybelsus are approved for type 2 diabetes, and Wegovy for weight management, with HFpEF under review ^[2]. That means whether a person can get the drug for heart failure symptoms specifically, and whether insurance will cover it for that reason, may depend on the approved use rather than on these trial results. Cash-pay options exist; one published listing shows introductory monthly prices of $199 for Ozempic or Wegovy injections and $149 for the Wegovy pill, with most ongoing fills at $299 to $349, depending on the drug and dose ^[2].

What happens next

Wegovy is currently under FDA review for HFpEF, and semaglutide is among the GLP-1 drugs that could gain approval for new uses including certain types of heart failure ^[2]. The available reports do not give a decision date. STEP-HFpEF DM is registered as NCT04916470 and was funded by Novo Nordisk ^[3].