What are the results of the Semaglutide (Glucagon-like peptide-1 receptor agonist) cardiovascular trial?

From the Guidelines

Semaglutide has demonstrated significant cardiovascular benefits in clinical trials, most notably in the SUSTAIN-6 trial, where injectable semaglutide (0.5mg or 1.0mg weekly) reduced major adverse cardiovascular events (MACE) by 26% compared to placebo in patients with type 2 diabetes at high cardiovascular risk 1. The results of the Semaglutide cardiovascular trial, specifically the SUSTAIN-6 trial, showed that semaglutide significantly reduced the risk of major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, compared to placebo in patients with type 2 diabetes at high cardiovascular risk. Key findings from the SUSTAIN-6 trial include:

• The primary outcome of cardiovascular death, nonfatal MI, or nonfatal stroke occurred in 108 patients (6.6%) in the semaglutide group vs. 146 patients (8.9%) in the placebo group (HR 0.74; 95% CI 0.58–0.95; P < 0.001) 1.
• More patients discontinued treatment in the semaglutide group because of adverse events, mainly gastrointestinal. The PIONEER 6 trial, which evaluated oral semaglutide, showed cardiovascular safety with a trend toward benefit, with a hazard ratio of 0.79 (95% CI 0.57–1.11; P < 0.001 for noninferiority) 1. For patients with type 2 diabetes and established cardiovascular disease or multiple risk factors, semaglutide should be considered as part of their treatment regimen, with the injectable form showing stronger cardiovascular outcome data than the oral formulation 1. Some of the benefits of semaglutide appear to extend beyond glycemic control and weight loss, likely involving improvements in blood pressure, lipid profiles, inflammation, and direct vascular effects 1. Overall, the evidence suggests that semaglutide is a valuable treatment option for patients with type 2 diabetes at high cardiovascular risk, with significant benefits in reducing major adverse cardiovascular events.

From the FDA Drug Label

The estimated hazard ratio for time to first MACE was 0.74 (95% CI: 0.58,0. 95). OZEMPIC significantly reduced the occurrence of MACE. Table 8. Treatment Effect for MACE and its Components, Median Study Observation Time of 2. 1 Years Placebo N=1649 (%) OZEMPIC N=1648 (%) Hazard ratio vs Placebo (95% CI)a Composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke (time to first occurrence) 146 (8.9) 108 (6.6) 0.74 (0.58,0.95)

The results of the Semaglutide cardiovascular trial, SUSTAIN 6, showed that Semaglutide significantly reduced the occurrence of Major Adverse Cardiovascular Events (MACE). The estimated hazard ratio for time to first MACE was 0.74 (95% CI: 0.58,0.95) 2.

• Key findings:
  • Reduced risk of non-fatal myocardial infarction
  • Reduced risk of non-fatal stroke
  • No significant effect on cardiovascular death The trial demonstrated the cardiovascular benefits of Semaglutide in patients with type 2 diabetes and established cardiovascular disease.

From the Research

Results of the Semaglutide Cardiovascular Trial

The results of the Semaglutide (Glucagon-like peptide-1 receptor agonist) cardiovascular trial are as follows:

• Semaglutide reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes at high risk of cardiovascular disease in a post hoc analysis of pooled data from the SUSTAIN 6 and PIONEER 6 trials 3.
• The hazard ratio of MACE from adding semaglutide to standard of care was 0.76 (95% CI 0.62-0.92) 3.
• Adding semaglutide to standard of care was associated with a mean increase of 1.7 (95% CI 0.5-2.9) life-years free of cardiovascular disease events 3.
• The estimated life-years free of cardiovascular disease gained with semaglutide was dependent on baseline risk and age at treatment initiation 3.
• Semaglutide reduced the risk of MACE vs comparators across the entire continuum of cardiovascular risk in a broad type 2 diabetes population 4.
• Semaglutide also reduced the risk of cardiovascular events in patients with preexisting cardiovascular disease and overweight or obesity but without diabetes 5.
• The primary cardiovascular end point, a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, occurred in 6.5% of patients in the semaglutide group and 8.0% of patients in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001) 5.

Key Findings

• Semaglutide has been shown to reduce the risk of adverse cardiovascular events in patients with diabetes 3, 6, 4.
• Semaglutide has also been shown to reduce the risk of cardiovascular events in patients without diabetes but with overweight or obesity and preexisting cardiovascular disease 5.
• The effects of semaglutide on cardiovascular risk are dependent on baseline risk and age at treatment initiation 3, 4.

Study Characteristics

• The SUSTAIN 6 and PIONEER 6 trials were post hoc analyses of pooled data from patients with type 2 diabetes at high risk of cardiovascular disease 3.
• The study by Husain et al. was a multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial of patients with preexisting cardiovascular disease and overweight or obesity but without diabetes 5.
• The study by Sorli et al. was a post hoc analysis of combined data from the SUSTAIN and PIONEER trials 4.