Semaglutide Linked to Improved Exercise Capacity, Weight Loss in Patients With HFpEF and Obesity

For patients with heart failure with preserved ejection fraction (HFpEF) and obesity, semaglutide treatment led to significant improvements in exercise capacity, weight loss, and a number of secondary end points in a study published in Clinical Cardiology.¹

Semaglutide was linked to improved exercise capacity and weight loss | Image credit: ID_Anuphon – stock.adobe.com

Semaglutide is a once‐weekly glucagon‐like peptide‐1 (GLP-1) receptor agonist, and 104 patients with HFpEF and obesity in this study received the drug while 214 patients received placebo. For those taking the GLP-1 agonist, treatment was initiated at a lower dose and escalated to 2.4 mg at week 16, and patients continued with the weekly dose until week 52. Most participants were female (54.1%) and the median age was 69 years.

Compared with placebo, using semaglutide was linked to significant improvements in exercise capacity, which was measured using the 6-minute walk distance test, with a mean difference of 15.1 meters between the 2 study arms (95% CI, 5.8-24.4; P = .002). Patients taking semaglutide also saw significantly more weight loss, losing 2.9% more body weight than those in the placebo group (95% CI, –4.1 to –1.7; P = .001).

The researchers also measured a significant reduction in C‐reactive protein (CRP) levels in the semaglutide group, with an estimated difference of 0.47 (95% CI, 0.32-0.62, P < .001) compared with the placebo group, suggesting the GLP-1 receptor agonist has an anti‐inflammatory effect on patients with HFpEF and obesity. The hierarchical composite end point, which included several health and function measures, also showed better outcomes linked to semaglutide use. About 55% of people in the semaglutide group had positive results compared with 46% in the placebo group, with an estimated ratio of 1.20 (95% CI, 0.92-1.56, P = .187).

Supportive secondary end points included changes in systolic blood pressure and waist circumference. While the differences were not statistically significant, the semaglutide group showed a trend toward lower systolic blood pressure (–1.8 mm Hg) and a smaller waist circumference (–6.7 cm). Additionally, at week 52, a significantly higher percentage of participants in the semaglutide group achieved body weight reductions of at least 10% (61.5%), at least 15% (49.2%), and at least 20% (28.7%) compared with the placebo group.

Exploratory end points included the percentage reduction in NT-proBNP levels, which showed a trend toward improvement in the semaglutide group (estimated ratio, 0.80; 95% CI, 0.56-1.14; P = .240). Additionally, the analysis of HF events over time indicated a lower incidence in the semaglutide group, although this finding was not statistically significant (HR, 0.23; 95% CI, 0.05-1.05, P = .075).

Looking at adverse events, the semaglutide group had a lower incidence of serious adverse events (6.7%) compared with the placebo group (7.9%). More participants in the semaglutide group discontinued treatment due to serious adverse events (14.3% vs 11.8%), although the different numbers of participants in each arm could be a factor in these differences.

Gastrointestinal issues were more common in the semaglutide group (14.3% vs 5.9%), and discontinuations due to these events were higher in this group (28.6% vs 5.9%). Fatal events were also more frequent in the semaglutide group (42.9% vs 29.4%). Cardiac disorders were reported in both groups but were more common in the placebo group (23.5% vs 14.3%). In the placebo arm, 2 patients reported atrial fibrillation and 2 reported cardiac failure during the study period, with no such reports from the treatment arm. Infections, gastrointestinal disorders, and a handful of other adverse events occurred at similar rates in both groups.

According to the researchers, past observational reports have suggested that a higher body mass index might be linked to better HF outcomes, a phenomenon known as the "obesity paradox."² However, these studies did not differentiate between unintentional weight loss—often linked to poor prognosis—and intentional weight loss through interventions. Small observational studies and a randomized trial on intentional weight loss in patients with HF and obesity showed associations with reduced symptom severity, improved functional status, and enhanced quality of life.³

“Our data extend these findings and show that weight loss with semaglutide (at a 2.4 mg dose) is a beneficial strategy for patients with HFpEF and obesity,” the researchers said.¹ “Future trials could explore whether similar benefits are achievable with different weight loss interventions or in other populations, such as those with heart failure and reduced ejection fraction and obesity.”

References

1. Rehman A, Saidullah S, Asad M, et al. Efficacy and safety of semaglutide in patients with heart failure with preserved ejection fraction and obesity. Clin Cardiol. 2024;47(5):e24283. doi:10.1002/clc.24283
2. Zamora E, Díez‐López C, Lupón J, et al. Weight loss in obese patientswith heart failure. J Am Heart Assoc. 2016;5(3):e002468. doi:10.1161/JAHA.115.00246823
3. Hundertmark MJ, Burrage M, Miller J, et al. Abstract 11064: intentional weight loss as a novel treatment for heart failure with preserved ejection fraction. Circulation. 2021;144:A11064. doi:10.1161/circ.144.suppl_1.1106424