STEP-HFpEF: semaglutide eased symptoms in obesity-related heart failure, and the effect held across ages

STEP-HFpEF asked whether semaglutide helps people who have both obesity and heart failure with preserved ejection fraction. After 52 weeks, the symptom score was 7.8 points better than on placebo, walking distance was 20.3 metres further, and body weight was 10.7 percentage points lower [1]. A later pooled analysis found the same pattern in younger and older people [2].

Why this study matters

Heart failure with preserved ejection fraction (HFpEF) is heart failure in which the heart still empties normally on each beat, yet the muscle is stiff and people are breathless and limited in what they can do. The trial authors describe it as increasingly common, with a high symptom burden, especially in people with obesity, and note that no therapy had been approved to target obesity-related HFpEF [1].

That made it a natural place to test a weight-loss drug. The question was practical: does losing weight on semaglutide change how people with this condition feel and function?

What they did

Participants were randomly assigned to once-weekly semaglutide 2.4 mg or placebo for 52 weeks. There were two dual primary end points: the change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS), where scores run from 0 to 100 and higher means fewer symptoms and physical limits, and the change in body weight [1].

Confirmatory secondary end points were the six-minute walk distance, a hierarchical composite end point, and the change in C-reactive protein, a blood marker of inflammation [1].

What they found

All four differences had p below 0.001 [1].

The hierarchical composite end point, which ranked participants on death, heart failure events, and then the changes in symptom score and walking distance, gave semaglutide a win ratio of 1.72 (95% CI 1.37 to 2.15) [1]. Serious adverse events were reported in 35 participants (13.3%) on semaglutide and 71 (26.7%) on placebo [1].

Does the effect depend on age?

Some clinicians have worried that older patients may gain less from this drug class, and perhaps risk more. A pre-specified pooled analysis of STEP-HFpEF and its companion trial in people who also had type 2 diabetes covered 1,145 participants in four age bands: under 55 (8.8%), 55 to 64 (23.3%), 65 to 74 (42.4%) and 75 or over (25.5%) [2].

Effects on symptom score (p for interaction 0.80) and body weight (0.41) were consistent across the bands, with no difference in the secondary end points, and the safety profile was consistent too [2]. With a quarter of participants aged 75 or over, the oldest group is not a footnote.

How much is 7.8 points?

The questionnaire runs from 0 to 100, with higher scores meaning fewer symptoms and physical limits [1]. Both groups improved: 16.6 points on semaglutide and 8.7 on placebo [1]. Placebo groups often improve in symptom-based trials, because people are followed closely and may expect to feel better, so the 7.8-point gap is the number to read, not the 16.6. The walking result is easier to picture. A 20.3-metre difference in six-minute walk distance is the extra ground covered in six minutes over placebo [1]. The abstract does not say whether either figure meets a threshold for a change that patients notice, so we do not claim one.

Caveats

• Sponsor-run. Novo Nordisk, which makes semaglutide, funded STEP-HFpEF [1]. The abstract of the pooled analysis does not state its funder.
• Symptoms and function, not outcomes. The primary end points measure how people feel and how much they weigh. They are not counts of hospital stays or deaths.
• The composite is mixed. It ranks death and heart failure events together with changes in symptom score and walking distance, so a win ratio of 1.72 does not mean 72% fewer events [1].
• Serious adverse events. The abstract gives the totals and not their causes, so the reason for the lower count is not stated.
• Weight and drug cannot be separated. Weight fell by about 13% on semaglutide, and the trial does not show how much of the symptom change came from that.
• One population. Everyone had HFpEF and a BMI of 30 or more, and the trial lasted 52 weeks.

What it means in practice

The result is consistent across the measures the trial tracked: symptoms, walking distance, weight and inflammation all moved the same way. The age analysis answers a specific worry, and the answer is that older participants did as well as younger ones [2].

Semaglutide is a prescription medicine, and heart failure treatment is managed by a cardiologist or heart failure team. Nothing here is a reason to change or stop an existing heart medicine. For related evidence, see our semaglutide guide and the SELECT cardiovascular trial.

What this means

We read STEP-HFpEF as good evidence that, in people with obesity and HFpEF, semaglutide improves how they feel and what they can do, and that age is not a reason to expect less. We are confident in the direction, because the weight, symptom, walking and inflammation results agree, and less sure how much of it is the weight loss itself. Take from it that this condition now has a randomised trial behind it. Do not take from it that semaglutide prevents hospital stays or deaths, because this trial did not measure that on its own.

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