BACKGROUND AND PURPOSE:

• As a treatment for overweight and obesity, semaglutide, a GLP-1 receptor agonist, can reduce the risk of cardiovascular disease in patients with diabetes
• Lincoff et al. (NEJM, 2023) assessed whether semaglutide also reduces the risk of major adverse cardiovascular events among patients with overweight or obesity and preexisting cardiovascular disease who did not have diabetes

METHODS:

• Multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial
• Participants
  • ≥45 years
  • Preexisting cardiovascular disease
  • BMI ≥27
  • No history of diabetes
• Interventions
  • Once-weekly subcutaneous semaglutide (2.4 mg/dose)
  • Placebo
• Primary outcome
  • Composite: Death from cardiovascular causes | Nonfatal myocardial infarction | Nonfatal stroke

RESULTS:

• Semaglutide: 8803 participants | Placebo: 8801
  • Mean duration of exposure: 34.2 (SD, 13.7) months
  • Mean duration of follow-up: 39.8 (SD, 9.4) months
• Primary cardiovascular end-point events were less common in the semaglutide group
  • Semaglutide: 6.5% | Placebo: 8.0%
  • Hazard ratio 0.80 (95% CI, 0.72 to 0.90) | P<0.001
• Adverse events that led to the permanent discontinuation of treatment occurred in more semaglutide patients than placebo patients
  • Semaglutide: 16.6% | Placebo: 8.2% | P<0.001

CONCLUSION:

• Semaglutide significantly reduced the incidence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke for patients with preexisting cardiovascular disease and overweight or obesity but without diabetes
• The authors state

An important limitation of this trial is that we included only patients with preexisting cardiovascular disease

The effects of semaglutide on primary prevention of cardiovascular events in persons with overweight or obesity but without previous atherosclerotic disease were not studied

Learn More – Primary Sources:

Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes