| Trial results
Short version: In a small randomized trial of 81 adults with heart failure with preserved ejection fraction (HFpEF) and obesity, 52 weeks of semaglutide 2.4 mg weekly lowered heart filling pressure, measured by catheter during light exercise, far more than placebo. More than half of treated patients no longer met the pressure definition of HFpEF.
What was reported
Mayo Clinic investigators published the CAMEO-SEMA trial in Nature Medicine on November 8, 2026 (Borlaug and colleagues). Participants had HFpEF, obesity and abnormally high filling pressures. They were randomized to semaglutide 2.4 mg weekly or placebo for 52 weeks. The main outcome was the change in pulmonary artery wedge pressure (PAWP) during light exercise. PAWP is a catheter measurement that works as a direct read on how congested the left side of the heart is.
| Measure at 52 weeks | Semaglutide | Placebo | Difference |
|---|---|---|---|
| Exercise PAWP, change | -9.8 mmHg | +0.9 mmHg | -10.6 mmHg (95% CI -13.3 to -8.0) |
| Resting PAWP | Not given in abstract | Not given in abstract | -7.1 mmHg (95% CI -9.8 to -4.4) |
| Hemodynamic remission* | 53.7% | 7.4% | Odds ratio 14.1 (95% CI 3.0 to 134.6) |
*Normal wedge pressure at both rest and exercise at week 52. Baseline wedge pressure averaged 17.5 mmHg at rest and 31.7 mmHg during exercise. Source: the Nature Medicine abstract.
The heart scan substudy
A second paper, published the same day, reports a prespecified cardiac MRI substudy in 49 of the participants (33 semaglutide, 16 placebo). Compared with placebo, semaglutide improved left atrial reservoir strain, the main MRI endpoint, and improved how the left ventricle fills. The authors also report lower left ventricular mass and better right ventricular function. Gains in the MRI measures tracked with the drop in exercise wedge pressure.
Why it matters
The earlier STEP-HFpEF trial showed semaglutide improved symptoms and weight in this group. It did not measure pressure inside the heart. This trial does, which points to a mechanism for the symptom benefit: less congestion under load.
What it does not show
- It is a small, single-center trial. ClinicalTrials.gov lists one site, in Rochester, Minnesota. Of 81 people randomized, 70 had paired pressure measurements at week 52.
- It measured pressures, not hospitalizations or deaths. No outcome in this trial says semaglutide prevents heart failure events.
- The remission confidence interval is very wide (3.0 to 134.6), so the size of that effect is uncertain.
- It is not a Novo Nordisk-run trial. Funding came from the US Department of Defense through the Congressionally Directed Medical Research Programs. Novo Nordisk supplied the semaglutide and placebo, and the lead author reports research grants and consulting fees from Novo Nordisk and consulting for Eli Lilly.
Related: Semaglutide medicine page | Wegovy | PeptideBlog semaglutide entry | PeptideBlog write-up of the trial
Source: Borlaug BA, et al. Hemodynamic effects of semaglutide in individuals with heart failure with preserved ejection fraction and obesity. Nature Medicine, November 8, 2026. doi:10.1038/s41591-026-04762-3 (peer-reviewed randomized trial).
Source: Ghanbari F, et al. Effects of semaglutide on cardiac structure and function in HFpEF and obesity: a prespecified cardiac MRI substudy of CAMEO-SEMA. Nature Medicine, November 8, 2026. doi:10.1038/s41591-026-04787-8 (peer-reviewed substudy, accepted manuscript posted early).
Source: ClinicalTrials.gov NCT05371496, Mayo Clinic. Registry record (lists Phase 4, 81 enrolled, completed July 17, 2026).