Does Rybelsus (semaglutide) have cardiovascular benefits?

Cardiovascular Benefits of Rybelsus (Oral Semaglutide)

Yes, Rybelsus (oral semaglutide) demonstrates significant cardiovascular benefits, including reduced risk of major adverse cardiovascular events in patients with established cardiovascular disease. 1

Established Cardiovascular Benefits

• Oral semaglutide has shown cardiovascular safety with evidence suggesting a similar cardiovascular profile to injectable semaglutide 2, 3
• The PIONEER 6 trial demonstrated cardiovascular safety of oral semaglutide with significant reductions in cardiovascular and overall mortality 3
• GLP-1 receptor agonists like semaglutide improve cardiovascular outcomes through multiple mechanisms:
  • Improved myocardial substrate utilization 1
  • Anti-inflammatory and anti-atherosclerotic effects 1
  • Reduced myocardial ischemia injury 1
  • Improved lipid profiles 1
  • Lowered systemic and pulmonary vascular resistance 1

Specific Cardiovascular Outcomes

• Semaglutide reduces the risk of major adverse cardiovascular events (MACE), including:
  • Cardiovascular death 1
  • Non-fatal myocardial infarction 1
  • Non-fatal stroke 1
• In the SELECT trial, semaglutide reduced the risk of cardiovascular death by 20% in patients with overweight or obesity 1
• In a large trial with over 17,600 participants with established cardiovascular disease, major cardiovascular events occurred in 6.5% of those treated with semaglutide compared to 8% in the placebo group 1

Cardiovascular Risk Factor Improvements

• Oral semaglutide provides additional cardiovascular benefits through:
  • Significant weight loss (average 9.8% reduction in body weight) 1
  • Reduced blood pressure 2, 4
  • Improved lipid profiles with reduced LDL-C 1, 2
  • Decreased inflammatory markers like C-reactive protein 1

Clinical Applications for Cardiovascular Risk Reduction

• Current guidelines recommend GLP-1 receptor agonists like oral semaglutide for:
  • Patients with type 2 diabetes with established atherosclerotic cardiovascular disease (ASCVD) 1
  • Patients at high risk for ASCVD 1
  • Patients with heart failure with preserved ejection fraction (HFpEF) and obesity 1

Ongoing Research

• The SOUL trial (Semaglutide cardiOvascular oUtcomes triaL) is evaluating the effects of oral semaglutide on cardiovascular outcomes in patients with type 2 diabetes and established ASCVD and/or chronic kidney disease 5
• This event-driven trial will continue until 1,225 first adjudication-confirmed MACEs have occurred 5

Considerations and Limitations

• Common side effects are primarily gastrointestinal:
  • Nausea and vomiting 1
  • Dyspepsia 1
  • Diarrhea 1
• Rare adverse effects include:
  • Risk of acute pancreatitis (caution in patients with history of pancreatitis) 1
  • Potential for cardiac arrhythmia/tachycardia (monitor if symptomatic) 1
• Slow dose titration helps improve gastrointestinal tolerability 1

Practical Prescribing Information

• Available in three doses (3,7, and 14 mg) to be gradually increased 4
• Must be taken on an empty stomach with no more than 4 oz of water, at least 30 minutes before the first food, beverage, or other oral medications of the day 4
• Insurance coverage may be restricted to FDA-approved indications (primarily type 2 diabetes) 1