From the Guidelines
Wegovy (semaglutide) should be considered for patients with heart failure with preserved ejection fraction (HFpEF), type 2 diabetes, and obesity, as it has been shown to improve symptoms related to heart failure and reduce body weight. The Semaglutide Treatment Effect in People with Obesity and HFpEF (STEP-HFpEF) trial, published in 2025 1, demonstrated that semaglutide improved symptoms related to heart failure, as measured by the Kansas City Cardiomyopathy Questionnaire clinical summary score, and reduced body weight by 9.8% compared to placebo.
Key Findings
- The STEP-HFpEF trial included 616 people with type 2 diabetes and a BMI of 30 or greater with HFpEF, who were assigned to receive once-weekly semaglutide at a dose of 2.4 mg or placebo 1.
- The primary end point was the change in the Kansas City Cardiomyopathy Questionnaire clinical summary score and the change in weight, with semaglutide showing a mean change in score of 13.7 points and a mean body weight reduction of 9.8% compared to placebo 1.
- Semaglutide treatment also improved 6-min walk distance and favored the composite end point of death, heart failure events, change in the Kansas City Cardiomyopathy Questionnaire clinical summary score, and C-reactive protein levels 1.
Clinical Implications
- The use of semaglutide in patients with heart failure and obesity or diabetes may provide additional benefits through weight reduction and improved glycemic control, which can indirectly help heart failure symptoms by reducing cardiac workload.
- However, any consideration of Wegovy in heart failure patients should be discussed with a cardiologist as part of a comprehensive treatment plan, as it would be an off-label use and individual patient factors must be carefully evaluated.
- Standard treatments for heart failure, such as ACE inhibitors, ARBs, beta-blockers, diuretics, aldosterone antagonists, and SGLT2 inhibitors, should still be prioritized, with semaglutide considered as an adjunctive therapy for patients with specific comorbidities.
From the Research
Wygovy for Heart Failure
- Wygovy, also known as semaglutide, has been studied for its effects on heart failure, particularly in patients with heart failure with preserved ejection fraction (HFpEF) 2, 3.
- In a pooled analysis of four randomized trials, semaglutide reduced the risk of cardiovascular death or worsening heart failure events in patients with HFpEF 2.
- The study found that semaglutide improved heart failure-related symptoms and physical limitations, and reduced the risk of worsening heart failure events, but had no significant effect on cardiovascular death alone 2.
- Another study found that semaglutide led to larger reductions in heart failure-related symptoms and physical limitations, and greater weight loss, compared to placebo, in patients with obesity-related HFpEF and type 2 diabetes 3.
- The use of semaglutide in patients with heart failure with reduced ejection fraction (HFrEF) is not well established, and current guidelines recommend the use of other medications, such as angiotensin receptor blockers, beta blockers, and sodium-glucose co-transporter 2 inhibitors, as first-line therapy 4, 5, 6.
- Overall, the available evidence suggests that semaglutide may be a useful therapy for patients with HFpEF, particularly those with obesity and type 2 diabetes, but further studies are needed to fully establish its efficacy and safety in this population 2, 3.