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STEP-HFpEF: semaglutide in heart failure with preserved ejection fraction and obesity

529 people with obesity and HFpEF heart failure, semaglutide 2.4 mg or placebo, 52 weeks. Symptoms up 16.6 vs 8.7 points; weight down 13.3 vs 2.6 percent.

2 min readUpdated September 4, 2026By FormBlends editorial team2 sourcesEducational, not medical advice

STEP-HFpEF: the trial at a glance

From the data
STEP-HFpEF at a glance: 529 randomised, 52 weeks, primary endpoint symptoms and weight.Four facts about STEP-HFpEF and its primary result: KCCQ-CSS change 16.6 versus 8.7 points (difference 7.8; 95% CI 4.8 to 10.9; P<0.001). Body weight -13.3% versus -2.6% (difference -10.7 percentage points; 95% CI -11.9 to -9.4; P<0.001).Randomised529Duration52 weeksPhase3ComparatorplaceboPrimary resultKCCQ-CSS change 16.6 versus 8.7 points (difference 7.8; 95% CI 4.8 to 10.9;P<0.001). Body weight -13.3% versus -2.6% (difference -10.7 percentage points;95% CI -11.9 to -9.4; P<0.001).
Figures as stated in the PubMed abstract. Primary endpoint: Dual primary: change in KCCQ clinical summary score (0 to 100, higher is better), and percent change in body weight, at week 52. Source: PubMed 37622681. Source: N Engl J Med 2023;389(12):1069-1084, PubMed 37622681.

Watch, with the fact-check

Clinical Trial Finds Weight Loss Medication Reduces Heart Events

Cleveland Clinic · 1:01 · uploaded 2023

What it gets right. A one-minute Cleveland Clinic clip in which a SELECT investigator states the headline: a roughly 20 percent relative reduction in major cardiovascular events in people with prior cardiovascular disease and overweight or obesity without diabetes.

What it leaves out. The transcript says 'over 177,000 patients'; the trial enrolled 17,604. Relative risk only, no absolute numbers, no adverse-event discontinuation figure.

Watch on YouTube

Embedded from YouTube (privacy-enhanced player, loads on click); verified against YouTube's oEmbed record on 2026-09-04. Nothing is rehosted. The fact-check is the FormBlends editorial team's reading, not the channel's endorsement.

STEP-HFpEF is a weight-management trial with a cardiology endpoint welded on. It is the first of the STEP programme to make a symptom score coprimary with weight.

What the trial asked

Whether semaglutide 2.4 mg reduces symptoms and physical limitations, and reduces body weight, in people who have both heart failure with preserved ejection fraction (HFpEF) and obesity.

Design

Randomised, placebo-controlled, once-weekly semaglutide 2.4 mg versus placebo for 52 weeks. Dual primary endpoints: change in the Kansas City Cardiomyopathy Questionnaire clinical summary score (KCCQ-CSS, 0 to 100, higher means fewer symptoms and limitations), and change in body weight.

Who was enrolled

529 patients with HFpEF and a BMI of 30 or higher. The abstract does not give age, sex or baseline weight.

Primary endpoint and result

EndpointSemaglutidePlaceboEstimated difference (95% CI)
KCCQ-CSS change+16.6 points+8.7 points7.8 (4.8 to 10.9)
Body weight change-13.3%-2.6%-10.7 points (-11.9 to -9.4)

P less than 0.001 for both.

Key secondary results

Confirmatory secondary endpoints, all P less than 0.001:

  • 6-minute walk distance: +21.5 m versus +1.2 m; difference 20.3 m (95% CI 8.6 to 32.1).
  • Hierarchical composite (death, heart-failure events, KCCQ-CSS and walk distance): win ratio 1.72 (95% CI 1.37 to 2.15) in favour of semaglutide.
  • C-reactive protein: -43.5 percent versus -7.3 percent; estimated treatment ratio 0.61 (95% CI 0.51 to 0.72).

Adverse events and discontinuation

Serious adverse events were reported in 35 participants (13.3 percent) on semaglutide and 71 (26.7 percent) on placebo. The abstract does not give discontinuation rates or itemise gastrointestinal events.

Funding and registration

Novo Nordisk. ClinicalTrials.gov NCT04788511.

What this trial does not show

  • It was not powered for death or hospitalisation. The hierarchical composite includes those events but is dominated by the symptom and walk-distance components.
  • Everyone had obesity. It says nothing about HFpEF in people of normal weight.
  • 52 weeks. Durability of the symptom benefit beyond that is not addressed.
  • It does not disentangle how much of the symptom improvement came through weight loss rather than another mechanism.

Where the numbers come from

PubMed abstract of the primary paper (PubMed 37622681), fetched 4 September 2026. For the hard-outcome cardiovascular trial in obesity without diabetes, see SELECT.

Sources (2)

  1. Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity (STEP-HFpEF). N Engl J Med 2023;389(12):1069-1084. PubMed 37622681 Accessed September 4, 2026.
  2. ClinicalTrials.gov NCT04788511 Accessed September 4, 2026.

Canonical URL: https://formblendsresearch.com/trials/step-hfpef. Written by the FormBlends editorial team. This page is educational and is not medical advice; see the medical disclaimer.