Does semaglutide (glucagon-like peptide-1 receptor agonist) improve heart muscle function?

Semaglutide Improves Heart Muscle Function in Patients with Obesity and Heart Failure

Yes, semaglutide has been shown to improve heart muscle function, particularly in patients with obesity-related heart failure with preserved ejection fraction (HFpEF). Recent evidence demonstrates significant cardiovascular benefits beyond just weight loss and glycemic control.

Cardiovascular Benefits of Semaglutide

Reduction in Major Adverse Cardiovascular Events

• Semaglutide significantly reduces the risk of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke in patients with type 2 diabetes 1
• The SUSTAIN-6 trial demonstrated that semaglutide reduced the primary cardiovascular outcome by 26% compared to placebo (HR 0.74 [95% CI 0.58–0.95]; P < 0.001) 1
• The SELECT trial showed that semaglutide 2.4 mg reduced MACE by 20% in patients with overweight/obesity without diabetes (HR 0.80; 95% CI 0.72-0.90; P<0.001) 2

Specific Heart Muscle Benefits

• In the STEP-HFpEF Program echocardiography substudy, semaglutide demonstrated significant improvements in cardiac structure and function 3:
  • Reduced left atrial volume (estimated mean difference -6.13 mL; 95% CI: -9.85 to -2.41 mL; P = 0.0013)
  • Prevented right ventricular enlargement (EMD in RV end-diastolic area: -1.99 cm²; 95% CI: -3.60 to -0.38 cm²; P = 0.016)
  • Improved diastolic function parameters including E-wave velocity and E/A ratio 3

Heart Failure Outcomes

• A pooled analysis of four randomized trials (SELECT, FLOW, STEP-HFpEF, and STEP-HFpEF DM) found that semaglutide reduced:
  • The combined endpoint of cardiovascular death or heart failure events by 31% (HR 0.69 [95% CI 0.53-0.89]; p=0.0045) 4
  • Worsening heart failure events by 41% (HR 0.59 [0.41-0.82]; p=0.0019) 4
• A meta-analysis showed semaglutide reduced hospitalization due to heart failure by 76% (RR 0.24 95% CI 0.12-0.57) 5

Mechanisms of Cardiac Benefit

• Semaglutide appears to provide cardiac benefits through multiple mechanisms 1:
  • Reduced myocardial work and filling pressures
  • Pre- and afterload reduction
  • Improved cardiovascular risk profile and lower blood pressure
  • Reduced atherogenesis
  • Upregulated nitric oxide and suppressed NF-κB activation 1

Clinical Implications

• Semaglutide is particularly beneficial for patients with:

  • Established cardiovascular disease and type 2 diabetes 1
  • Obesity-related heart failure with preserved ejection fraction 4, 3
  • Overweight/obesity without diabetes but with cardiovascular risk 2

• Benefits appear consistent across heart failure subtypes:

  • Effective in both heart failure with reduced ejection fraction (HR 0.65,95% CI 0.49-0.87 for MACE) and heart failure with preserved ejection fraction (HR 0.69,95% CI 0.51-0.91 for MACE) 6

Safety Considerations

• Common adverse events with semaglutide are primarily gastrointestinal 1, 2
• Higher discontinuation rates due to adverse events compared to placebo (16.6% vs. 8.2% in SELECT trial) 2
• Use with caution in patients with:
  • History of pancreatitis
  • Severe renal impairment
  • Prior gastric surgery 1

Bottom Line

Semaglutide demonstrates significant cardiovascular benefits beyond glycemic control and weight loss, with recent evidence showing direct improvements in cardiac structure and function. The drug appears to be particularly beneficial in patients with obesity-related heart failure, where it can reduce adverse cardiac remodeling and improve clinical outcomes.