Is Ozempic (semaglutide) advised for patients with a history of cardiovascular disease and no diabetes?

Ozempic (Semaglutide) for Patients with Cardiovascular Disease Without Diabetes

Semaglutide is strongly advised for patients with a history of cardiovascular disease without diabetes based on recent evidence showing significant reduction in major adverse cardiovascular events. 1

Evidence Supporting Semaglutide Use in Non-Diabetic CVD Patients

Cardiovascular Outcomes

• The SELECT trial demonstrated that weekly subcutaneous semaglutide 2.4 mg reduced the risk of major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) by 20% compared to placebo (HR 0.80; 95% CI, 0.72-0.90; P<0.001) in patients with pre-existing cardiovascular disease who were overweight or obese but without diabetes 2, 1
• The real-world SCORE study confirmed these benefits, showing significantly lower risks of revised 3-point MACE (HR 0.43; p<0.001) and revised 5-point MACE (HR 0.55; p<0.001) in non-diabetic patients with atherosclerotic cardiovascular disease and overweight/obesity who were initiated on semaglutide 2.4 mg 3
• Cardiovascular benefits of semaglutide were consistent across all baseline HbA1c subgroups (<5.7%, 5.7% to <6.0%, and 6.0% to <6.5%) in non-diabetic patients, indicating that glycemic status does not affect cardioprotective benefits 4

Weight Management Benefits

• Semaglutide produced sustained weight loss in patients with cardiovascular disease and obesity/overweight without diabetes, with mean reductions of 10.2% in body weight, 7.7 cm in waist circumference, and 6.9% in waist-to-height ratio at 208 weeks compared to minimal changes with placebo 5
• Weight loss was clinically significant across all demographic groups and BMI categories, and was maintained for up to 4 years 5
• The 2024 ESC guidelines for chronic coronary syndromes specifically mention that pharmacological treatment with GLP-1 receptor agonists may be considered for weight reduction in patients who don't reach weight targets through lifestyle modifications 2

Safety Considerations

• In the SELECT trial, adverse events leading to discontinuation were more common with semaglutide (16.6%) than placebo (8.2%), primarily due to gastrointestinal side effects 1
• Discontinuation rates were inversely related to BMI class, with higher discontinuation rates in patients with lower BMI 5
• Despite higher discontinuation rates, semaglutide was associated with fewer serious adverse events across all BMI categories compared to placebo 5
• The FDA label for semaglutide notes it has not been studied in patients with a history of pancreatitis, so caution is warranted in this population 6

Cost-Effectiveness Considerations

• Cost-effectiveness analysis shows an incremental cost-effectiveness ratio of $72,962 per QALY gained for semaglutide compared to standard care in patients with obesity/overweight and cardiovascular disease without diabetes 7
• Price reduction by 50% would improve cost-effectiveness to $37,190 per QALY gained, making it more economically attractive for healthcare systems 7

Clinical Algorithm for Patient Selection

1. Identify appropriate candidates:

   • Patients with established cardiovascular disease 2, 1
   • BMI ≥27 kg/m² (overweight or obese) 1
   • No history of diabetes 1
   • Particularly beneficial for those who have not achieved weight targets through lifestyle modifications 2

2. Dosing and administration:

   • Semaglutide 2.4 mg subcutaneously once weekly (the dose studied in SELECT trial) 1
   • Consider dose escalation protocol to minimize gastrointestinal side effects

3. Monitoring:

   • Regular assessment of cardiovascular outcomes
   • Weight and anthropometric measurements
   • Tolerance of medication, particularly gastrointestinal side effects
   • Screen for development of diabetes

Conclusion

Based on the most recent and highest quality evidence, particularly the SELECT trial published in the New England Journal of Medicine, semaglutide 2.4 mg once weekly is strongly recommended for patients with established cardiovascular disease who are overweight or obese but do not have diabetes. The 2024 ESC guidelines for chronic coronary syndromes support this recommendation, acknowledging the significant reduction in cardiovascular events with semaglutide in this population.