STEP-HFpEF DM extends heart failure benefit to people with type 2 diabetes

A companion trial called STEP-HFpEF DM found that semaglutide improved heart failure symptoms and produced greater weight loss than placebo in adults with obesity-related heart failure with preserved ejection fraction (HFpEF) who also have type 2 diabetes ^[1]. The 616 participants were randomly assigned to receive once-weekly semaglutide at 2.4 mg or a placebo for 52 weeks ^[1]. This trial extends findings from an earlier study in people without diabetes, confirming the same general pattern of benefit in a group whose disease is often harder to treat ^[1].

The trial measured symptoms and physical limits using the Kansas City Cardiomyopathy Questionnaire clinical summary score, a 0-to-100 scale where higher numbers mean fewer symptoms ^[1]. People taking semaglutide improved by an average of 13.7 points, compared with 6.4 points for those on placebo, a difference of 7.3 points ^[1]. Body weight fell by 9.8% on average with semaglutide versus 3.4% with placebo, a gap of 6.4 percentage points ^[1].

Other measures also favored semaglutide. Participants on the drug walked 14.3 meters farther in six minutes than those on placebo ^[1]. A combined ranking of death, heart failure events, and changes in symptoms and walking distance favored semaglutide, with a win ratio of 1.58 ^[1]. A blood marker of inflammation called C-reactive protein dropped more in the semaglutide group, with a treatment ratio of 0.67 ^[1]. Serious adverse events were reported in 17.7% of people on semaglutide, compared with 28.8% of those on placebo ^[1].

The trial was funded by Novo Nordisk, the maker of semaglutide, and is registered as NCT04916470 ^[1]. Because HFpEF has no approved therapies specifically aimed at obesity-related cases in people with type 2 diabetes, the trial addressed an unmet gap in a difficult-to-treat form of heart disease ^[1]. A pooled analysis combining this trial with the earlier STEP-HFpEF study, which enrolled people without diabetes, has also been published, looking at results across both groups together ^[1].

Why it matters for patients

For people with type 2 diabetes who also have obesity-related HFpEF, this trial suggests that semaglutide may ease breathlessness, fatigue, and physical limits linked to heart failure, not just help with weight or blood sugar ^[1]. The reported drop in serious adverse events in the semaglutide group, compared with placebo, may also matter to patients weighing the medication's overall safety profile, though the sources do not break down which types of adverse events were most affected ^[1].

Heart failure with preserved ejection fraction is a form of heart failure where the heart's main pumping chamber squeezes normally but does not relax and fill properly, and it is closely tied to obesity and diabetes ^[1]. Because no therapy had been specifically approved for obesity-related HFpEF in people with diabetes before this trial, the results fill a gap for a population that doctors have historically had fewer targeted options to treat ^[1].

Patients should know this was a 52-week trial funded by the drug's manufacturer, and the sources do not address outcomes beyond one year ^[1]. The sources also do not specify how these findings translate into official prescribing guidance or insurance coverage decisions for this specific patient group ^[1].

What happens next

The original findings were published in The New England Journal of Medicine, with follow-up commentary appearing in the same journal in July 2024 ^[1]. A separate pooled analysis combining data from this trial and the earlier STEP-HFpEF study, which excluded diabetes, has already been published in The Lancet, offering a broader look at semaglutide's effect on obesity-related HFpEF overall ^[1]. The sources do not describe any additional planned trials or specific regulatory decisions tied to these results.