STEP-HFpEF DM extends the heart failure finding to type 2 diabetes

A large clinical trial called STEP-HFpEF DM found that semaglutide, the medicine sold as Wegovy for weight loss and Ozempic for diabetes, improved heart failure symptoms and produced meaningful weight loss in people who have both obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes ^[3]. Results were presented at the American College of Cardiology's 2024 meeting and published in the New England Journal of Medicine ^[3].

The trial randomly assigned 616 participants with HFpEF, a body-mass index of 30 or higher, and type 2 diabetes to receive once-weekly semaglutide at 2.4 mg or a placebo for 52 weeks ^[3]. On the Kansas City Cardiomyopathy Questionnaire, a standard tool that scores heart failure symptoms and physical limitations from 0 to 100, participants on semaglutide gained 13.7 points on average, compared with 6.4 points for those on placebo, a difference of 7.3 points ^[3]. Body weight fell 9.8% with semaglutide versus 3.4% with placebo, a 6.4 percentage-point gap ^[3]. Participants on the drug also walked 14.3 meters farther on a six-minute walk test than those on placebo, and a composite measure combining death, heart failure events, and symptom and walking changes favored semaglutide, with a win ratio of 1.58 ^[3]. A marker of inflammation, C-reactive protein, dropped more with semaglutide as well ^[3]. Serious adverse events were less common with semaglutide, occurring in 17.7% of that group versus 28.8% of the placebo group ^[3].

These results extend an earlier finding. A companion trial, STEP-HFpEF, tested the same drug and dose in 529 people with obesity-related HFpEF but without diabetes, and it excluded anyone with a history of diabetes ^[1]. In that group, the KCCQ symptom score improved by 16.6 points with semaglutide versus 8.7 with placebo, and body weight fell 13.3% versus 2.6% ^[1]. The six-minute walk distance improved by 20.3 meters more with semaglutide, and serious adverse events were lower with the drug, 13.3% versus 26.7% ^[1]. The benefit on symptoms and weight loss was somewhat smaller in the diabetes trial than in the non-diabetes trial, though both showed clear improvement over placebo ^[1][3].

Why it matters for patients

Heart failure with preserved ejection fraction is a form of heart failure where the heart's pumping chamber works normally but the heart still cannot fill or relax properly, and it is closely linked to obesity ^[1]. People with this condition and obesity often have more severe symptoms and worse quality of life than those without excess weight ^[1]. Until these trials, no therapy had been approved specifically to target obesity-related HFpEF ^[1].

For patients who have both HFpEF and type 2 diabetes, a group that carries extra symptom burden, these results suggest semaglutide could ease breathlessness, fatigue, and physical limitations while also producing weight loss, on top of its already established uses for blood sugar control and weight management. But it is important to be clear about what has and has not happened. Wegovy is not approved by the Food and Drug Administration specifically for heart failure ^[2]. As of this trial's publication, Wegovy was reported to be under FDA review for an HFpEF indication ^[2], meaning the agency has not yet granted approval for doctors to prescribe it for that specific purpose. Patients currently taking semaglutide for diabetes or weight loss should not assume it is officially sanctioned for heart failure treatment based on these trial results alone.

Both trials were funded by Novo Nordisk, the maker of semaglutide ^[1][3], which is a detail worth keeping in mind when weighing how the results are presented.

What happens next

The sources do not specify a decision date for an FDA ruling on a heart failure indication for Wegovy. Patients and clinicians will need to watch for a formal FDA decision before this use becomes an approved indication ^[2].