Summary
In a 52-week placebo-controlled trial of 81 people with obesity and HFpEF, semaglutide lowered pulmonary artery wedge pressure at rest and during exercise. More than half of participants assigned semaglutide met the study’s definition of hemodynamic remission.
A double-blind, placebo-controlled trial published in Nature Medicine found that semaglutide lowered heart-filling pressures in people with heart failure with preserved ejection fraction (HFpEF) and obesity. Among 81 participants randomly assigned to weekly semaglutide 2.4 mg or placebo for 52 weeks, the reduction in pulmonary artery wedge pressure during low-intensity exercise was substantially greater with semaglutide.
HFpEF is a form of heart failure in which the heart’s pumping fraction remains preserved, even though the heart does not fill and function normally. The trial examined pulmonary artery wedge pressure (PAWP), an invasively measured indicator of pressure in the heart’s left-sided filling system and cardiac congestion.
Exercise and resting pressures fell with semaglutide
At the start of the study, mean PAWP was 17.5 mmHg at rest and 31.7 mmHg during exercise. After 52 weeks, exercise PAWP fell by a mean of 9.8 mmHg in the semaglutide group, while it rose by 0.9 mmHg with placebo. The estimated difference between groups was −10.6 mmHg (95% confidence interval −13.3 to −8.0; P < 0.0001).
Semaglutide was also associated with lower resting PAWP than placebo at 52 weeks: the estimated between-group difference was −7.1 mmHg (95% confidence interval −9.8 to −4.4; P < 0.0001). The trial’s primary outcome focused on pressure during low-intensity exercise, where heart failure-related filling problems can become more apparent.
The researchers defined hemodynamic remission as normal PAWP at both rest and exercise at week 52. This was reported in 53.7% of participants assigned semaglutide and 7.4% assigned placebo. The estimated odds ratio was 14.1, with a 95% confidence interval of 3.0 to 134.6.
What the measurements add
The trial provides direct physiological evidence that semaglutide treatment can reduce measured filling pressures in people with both HFpEF and obesity. That helps investigate how the drug may affect the heart’s response to rest and exercise, beyond measuring symptoms or body weight alone.
The findings come from a relatively small trial of 81 participants followed for 52 weeks, and the results apply directly to the studied group: people with HFpEF and obesity. The principal outcome was an invasive pressure measurement, rather than a long-term clinical event. The reported hemodynamic results show a change in pressure but do not identify the biological pathway responsible for it.