Semaglutide 2.4mg is a breakthrough treatment that has demonstrated significant cardiovascular benefits for overweight adults, according to the results of the SELECT trial. The trial involved adults with preexisting heart disease who were overweight or obese but did not have diabetes. The study found that treatment with semaglutide 2.4mg was superior to placebo in reducing the risk of cardiovascular events.
The SELECT trial is a milestone in weight management therapy as it is the first time a treatment has been proven to reduce cardiovascular risk in overweight individuals through a rigorous randomized controlled trial. This establishes overweight and obesity as modifiable risk factors for cardiovascular disease and expands the potential application of semaglutide 2.4mg to a broader population of patients with both overweight/obesity and cardiovascular disease.
Semaglutide, in its 1mg injection form, was previously approved by the FDA for the treatment of type 2 diabetes. In 2021, semaglutide 2.4mg received approval for chronic weight management in adults with obesity and at least one weight-related comorbidity. The SELECT trial adds to the existing evidence of the safety and cardiovascular benefits of semaglutide in people with diabetes and extends it to people with obesity.
The SELECT trial was designed to evaluate whether once-weekly semaglutide 2.4mg could reduce the incidence of major adverse cardiovascular events in a population of 17,604 adults with preexisting heart disease and overweight/obesity but no diabetes. Over a follow-up period of nearly 40 months, the trial found that the primary cardiovascular endpoint event occurred in 6.5% of patients receiving semaglutide 2.4mg compared to 8% of patients on placebo. The difference in event rates between the two groups emerged early in the study, within the first few months.
The researchers also observed consistent trends for each component of the composite primary outcome, as well as reductions in coronary revascularization and kidney function deterioration among those on semaglutide 2.4mg. Moreover, patients in the semaglutide group experienced a mean weight loss of 9.4% after 104 weeks, compared to 0.9% in the placebo group. Waist circumference also decreased significantly in the semaglutide group.
Although the trial participants did not have diabetes at baseline, the researchers noted a reduction in the progression to diabetes and prediabetes with semaglutide 2.4mg. The percentage of patients who developed diabetes during the follow-up period was 3.5% in the semaglutide group compared to 12% in the placebo group. Progression to prediabetes was also lower in the semaglutide group.
In terms of safety, serious adverse events were less frequent in the semaglutide group, with reduced rates of cardiac disorders and infectious events. Adverse events leading to discontinuation of the study drug occurred more frequently in the semaglutide group, primarily due to differences in gastrointestinal side effects. However, there were no significant increases in adverse events of special interest, such as acute pancreatitis and gallbladder-related events, cancers, or psychiatric disorders.
The SELECT trial, conducted at 804 sites in 41 countries, is the largest and longest trial to date for this group of patients. However, the lack of a globally representative patient population and underrepresentation of women and people of Black ethnicity limit the generalizability of the findings. Furthermore, the results cannot be extrapolated to individuals with obesity who do not have a history of heart disease.
The findings of the SELECT trial signify a turning point in the treatment of obesity and cardiovascular disease. The rapid transformation of obesity treatment is evident from the recent approvals of highly effective anti-obesity medications. However, it is important to go beyond weight reduction and prioritize the treatment of obesity to improve health outcomes in people with cardiovascular disease.
With the global prevalence of obesity expected to reach 1 billion by 2030, addressing obesity as a modifiable risk factor for cardiovascular disease is crucial. The breakthrough results of the SELECT trial highlight the potential of semaglutide 2.4mg to reduce cardiovascular risk in overweight individuals and pave the way for further research and development in the field of obesity treatment and cardiovascular health.
