Semaglutide improves symptoms and function in obesity-related heart failure

1. Semaglutide showed significant improvements in KCCQ-CSS score and reduction in body weight compared to placebo.

2. There were fewer serious adverse events in the semaglutide group.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Obesity and diabetes lead to poor prognosis in patients with heart failure. GLP-1 receptor agonists, such as semaglutide, have been shown to mitigate this effect, however, most studies have been in patients with co-morbid diabetes and obesity. Few studies to date have evaluated the use of GLP-1 receptor agonists in patients without diabetes who have obesity-related heart failure. This randomized controlled trial aimed to assess the safety and efficacy of semaglutide in patients who had heart failure with preserved ejection fraction (HFpEF). The primary outcome was mean change in Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) and body weight, while a key secondary outcome was change in 6-minute walk distances. According to study results, significant improvements in KCCQ-CSS, bodyweight reduction, and 6-minute walk distance were noted in the semaglutide group compared with placebo. Although this study was well done, it was limited by the potential for unmeasured confounding factors influencing the outcomes.

Click to read the study in The Lancet

Relevant Reading: Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes

In-depth [randomized controlled trial]: Between Mar 19, 2021, and Mar 9, 2022, 1869 patients were screened for eligibility across 129 clinical research sites in 18 countries. Included were patients ≥ 18 years of age with known HFpEF (left ventricular ejection fraction ≥ 45%), BMI ≥ 30 kg/m², and NYHA class II–IV symptoms. Altogether, 1145 patients (573 in semaglutide and 572 in placebo) were included in the final analysis. Mean improvement in KCCQ-CSS score (between-group difference of 7.5 points for KCCQ-CSS, 95% confidence interval [CI] 5.3-9.8, p<0.0001) and reduction in body weight (-8.4%, 95% CI -9.2 to -7.5, p<0.0001) was significantly greater in semaglutide than placebo. Furthermore, the 6-minute walk distance was also improved in the semaglutide group (mean difference 17.1 meters, 95% CI 9.2 to 25.0). There were fewer serious adverse events in the semaglutide group compared to control (161 vs. 301). Findings from this study suggest that semaglutide improves heart failure-related symptoms and body weight in patients with obesity-related HFpEF.

Image: PD

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