Cardiovascular Benefits of Semaglutide - Clinical Trial Interpretation

A recent study published in the international journal Diabetes Care, titled "Semaglutide and Cardiovascular Outcomes by Baseline HbA1c and Change in HbA1c in People With Overweight or Obesity but Without Diabetes in SELECT," has revealed a new benefit of Semaglutide - the cardiovascular benefits. Researchers from the University of Texas Southwestern Medical Center and other institutions have demonstrated that Semaglutide can reduce cardiovascular events in overweight and obese individuals with established atherosclerotic cardiovascular disease (ASCVD) but without diabetes, regardless of their baseline glycated hemoglobin (HbA1c) levels.

Study Design and Recruitment

The study design involved randomizing participants (overweight or obese non-diabetic patients with confirmed ASCVD) into two groups (1:1): one receiving 2.4 mg of semaglutide weekly with ascending doses from 0.24 mg to 0.5, 1.0, 1.7, and finally 2.4 mg, and the other receiving a placebo. This approach aimed to evaluate the independent cardiovascular effects of semaglutide.

The research included 17,604 participants with varying baseline HbA1c levels: below 5.7%, between 5.7%-6.0%, and 6.0%-6.5% based on the guidance of the American Diabetes Association and the International Expert Committee.

Results

Results showed that semaglutide exhibited significant cardiovascular protective effects across all initial HbA1c levels. It effectively reduced the incidence of first major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, and stroke. Notably, this protective effect was particularly pronounced in terms of all-cause mortality. The benefits of semaglutide were consistent across subgroups with different HbA1c changes. The following graphs show the cardiovascular benefits of Semaglutide from the trial in terms of four end points. Specifically, MACE was defined as a composite of mortality from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke. Expanded MACE was defined as mortality from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke; coronary revascularization; or hospitalization for unstable angina. Heart failure composite was defined as mortality from cardiovascular causes, or hospitalization or urgent medical visit for heart failure. Cumulative incidence estimates are based on time from randomization to the first occurrence of each end point. 

Time to first cardiovascular event for three-point MACE, expanded MACE, all-cause mortality, and heart failure composite in the SELECT trials by baseline HBA1C subgroups. Modified from the original article. 

As the research artical highlights: "In people with overweight or obesity and preexisting cardiovascular disease, semaglutide is expected to exert cardiovascular benefits even among those with normoglycemia and such benefits are likely due to pleiotropic factors besides semaglutide's glucose-lowering capacity."

Conclusion

In conclusion, this study provides strong evidence that in overweight or obese non-diabetic patients with ASCVD, semaglutide not only significantly reduces the risk of cardiovascular events but does so independently of baseline HbA1c levels or changes in HbA1c. These findings open new avenues for the application of semaglutide in cardiovascular disease prevention and treatment, particularly for individuals with normal blood glucose levels but high cardiovascular risk, potentially offering a new tool in maintaining cardiovascular health.

About Unibest

As we conclude our analysis of the SELECT trial and Semaglutide's cardiovascular benefits, we at Unibest hope this interpretation has provided valuable insights for your decision-making process (use this link to find Unibest's Semaglutide offering). Our Clinical Trial Interpretation Series aims to be a trusted resource in your pursuit of pharmaceutical innovation. By offering these concise yet comprehensive analyses, we strive to support you in staying ahead in a rapidly evolving industry. Remember, at Unibest, we're not just sharing information – we're empowering you with knowledge to drive the future of pharmaceutical care. Stay tuned for our next edition, where we'll continue to bring you cutting-edge research interpretations to inform and enhance your product portfolio.

References