3 Key Takeaways
Plain English Summary- 01Core Finding
Here, in this double-blind, placebo (inactive comparison treatment)-controlled trial, we randomly assigned 81 patients (47 women) with HFpEF and obesity to semaglutide (2.4 mg weekly) or placebo for 52 weeks.
- 02Study Evidence
Tested in a randomized controlled trial (81 patients) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
What This Means for You
After 52 weeks, the mean change in PAWP during exercise was -9.8 (a clinically meaningful level confidence interval (CI): -11.3 to -8.2) mmHg with semaglutide and +0.9 (a clinically meaningful level CI: -1.3 to 3.0) mmHg with placebo (estimated difference, -10.6 mmHg; a clinically meaningful level CI: -13.3 to -8.0; P < 0.0001). As compared to placebo (inactive comparison treatment), semaglutide also decreased resting PAWP (estimated difference, -7.1 mmHg; a clinically meaningful level CI: -9.8 to -4.4; P < 0.0001), and semaglutide-treated patients were more likely to experience hemodynamic remission (a clinically meaningful level versus 7.4%, odds ratio = 14.1, a clinically meaningful level CI: 3.0-134.6, P < 0.001). The results from this trial indicate that, in patients with HFpEF and obesity, treatment with semaglutide reduced left heart filling pressures during exercise and at rest and was associated with hemodynamic HFpEF remission in over half of treated patients. ClinicalTrials.gov identifier: NCT05371496.
The Discovery
The glucagon-like peptide-1 receptor agonist semaglutide improves symptoms in heart failure with preserved ejection fraction (HFpEF) through unclear mechanisms. Here, in this double-blind, placebo (inactive comparison treatment)-controlled trial, we randomly assigned 81 patients (47 women) with HFpEF and obesity to semaglutide (2.4 mg weekly) or placebo for 52 weeks. The primary outcome was the change in invasively measured pulmonary artery wedge pressure (PAWP), a direct measure of cardiac congestion, during low-intensity exercise. Additional mechanistic outcomes included other hemodynamic measures and hemodynamic HFpEF remission (defined as normal PAWP under conditions of both rest and exercise at 52 weeks). At baseline, PAWP was 17.5 ± 4.3 mmHg at rest and 31.7 ± 5.2 mmHg during exercise. After 52 weeks, the mean change in PAWP during exercise was -9.8 (a clinically meaningful level confidence interval (CI): -11.3 to -8.2) mmHg with semaglutide and +0.9 (a clinically meaningful level CI: -1.3 to 3.0) mmHg with placebo (estimated difference, -10.6 mmHg; a clinically meaningful level CI: -13.3 to -8.0; P < 0.0001).
How It Works, Simply
This pharmacology research focuses on receptor targeting. Researchers evaluated it using a randomized controlled trial (81 patients) at the randomized clinical trial stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
Here, in this double-blind, placebo-controlled trial, we randomly assigned 81 patients (47 women) with HFpEF and obesity to semaglutide (2.4 mg weekly) or placebo for 52 weeks.
- 02Study Evidence
Tested in a randomized controlled trial (81 patients) at the randomized clinical trial stage.
- 03Practical Meaning
Controlled trial findings show causal benefit under protocol rules; real-world effectiveness can vary across patients.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Randomized controlled trial
Randomized controlled trial (81 patients) · Randomized Clinical Trial
Biological Pathway & Modality
Receptor targeting
Intervention: Hemodynamic effects of semaglutide in individuals with heart failure with preserved
Experimental Findings & Endpoints
The glucagon-like peptide-1 receptor agonist semaglutide improves symptoms in heart failure with preserved ejection fraction (HFpEF) through unclear mechanisms.
Here, in this double-blind, placebo-controlled trial, we randomly assigned 81 patients (47 women) with HFpEF and obesity to semaglutide (2.4 mg weekly) or placebo for 52 weeks. The primary outcome was the change in invasively measured pulmonary artery wedge pressure (PAWP), a direct measure of cardiac congestion, during low-intensity exercise.
Additional mechanistic outcomes included other hemodynamic measures and hemodynamic HFpEF remission (defined as normal PAWP under conditions of both rest and exercise at 52 weeks). At baseline, PAWP was 17.5 ± 4.3 mmHg at rest and 31.7 ± 5.2 mmHg during exercise.
After 52 weeks, the mean change in PAWP during exercise was -9.8 (a clinically meaningful level confidence interval (CI): -11.3 to -8.2) mmHg with semaglutide and +0.9 (a clinically meaningful level CI: -1.3 to 3.0) mmHg with placebo (estimated difference, -10.6 mmHg; a clinically meaningful level CI: -13.3 to -8.0; P < 0.0001).
Clinical Translation & Practice Context
After 52 weeks, the mean change in PAWP during exercise was -9.8 (a clinically meaningful level confidence interval (CI): -11.3 to -8.2) mmHg with semaglutide and +0.9 (a clinically meaningful level CI: -1.3 to 3.0) mmHg with placebo (estimated difference, -10.6 mmHg; a clinically meaningful level CI: -13.3 to -8.0; P < 0.0001).
As compared to placebo, semaglutide also decreased resting PAWP (estimated difference, -7.1 mmHg; a clinically meaningful level CI: -9.8 to -4.4; P < 0.0001), and semaglutide-treated patients were more likely to experience hemodynamic remission (a clinically meaningful level versus 7.4%, odds ratio = 14.1, a clinically meaningful level CI: 3.0-134.6, P < 0.001). The results from this trial indicate that, in patients with HFpEF and obesity, treatment with semaglutide reduced left heart filling pressures during exercise and at rest and was associated with hemodynamic HFpEF remission in over half of treated patients.
ClinicalTrials.gov identifier: NCT05371496.
The Bottom Line · Clinical Pearl
“ClinicalTrials.gov identifier: NCT05371496 .”
Published in Nature Medicine · Current Stage: Randomized Clinical Trial