Semaglutide and Exercise Function in Obesity-Related HFpEF: Insights From the STEP-HFpEF Program

Area of Science:

• Cardiology
• Metabolic Diseases
• Clinical Trials

Background:

• Exercise function, measured by 6-minute walk distance (6MWD), is significantly limited in patients with heart failure with preserved ejection fraction (HFpEF).
• Impaired exercise capacity in HFpEF is linked to factors including obesity, inflammation, and congestion.

Purpose of the Study:

• To analyze factors associated with baseline exercise function in HFpEF.
• To evaluate the effects of semaglutide on 6MWD and other clinical endpoints in patients with HFpEF, stratified by baseline 6MWD.

Main Methods:

• Pooled data analysis from the STEP-HFpEF Program involving 1,145 patients randomized to semaglutide or placebo.
• Assessment of baseline 6MWD correlates and semaglutide's impact on 6MWD at 20 and 52 weeks.
• Contrast of semaglutide's effects on primary and secondary endpoints across tertiles of baseline 6MWD.

Main Results:

• Patients with lower baseline 6MWD exhibited higher BMI, inflammation (C-reactive protein), and congestion (NT-proBNP).
• Semaglutide significantly increased 6MWD versus placebo at 20 weeks (14.6 m) and 52 weeks (17.1 m), with consistent effects across subgroups.
• Semaglutide improved KCCQ-CSS, reduced body weight and inflammation, and positively impacted a composite endpoint, with greater weight loss correlating to larger 6MWD gains.

Conclusions:

• In obesity-related HFpEF, reduced 6MWD is strongly associated with adiposity, inflammation, and congestion.
• Semaglutide demonstrated consistent improvements in HFpEF symptoms, physical limitations, and exercise function across the 6MWD spectrum, evident by 20 weeks and preceding maximal weight loss.
• The study highlights semaglutide's efficacy in improving exercise capacity and quality of life in HFpEF patients, with benefits linked to weight reduction.