The SELECT Study

The SELECT Study

January 2, 2024

December 2023 Letter from the Director

The use of anti-obesity medications has risen dramatically in the last year.  Both tirzepatide and semaglutide are on the market for weight loss and weight management, and the demand for GLP-1 receptor agonists for obesity will likely continue to rise. Research is now catching up on the beneficial outcomes in addition to weight loss for patients taking anti-obesity medications. 

 In November, the results of the SELECT trial on Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes were presented at the American Heart Association’s conference and concurrently released in the New England Journal of Medicine. This trial was the first to demonstrate the impacts of anti-obesity medications on more than just weight loss. The study showed that patients with pre-existing cardiovascular disease who received subcutaneous once-weekly 2.4mg semaglutide demonstrated a 20% reduction in major adverse cardiac events (MACEs) over a period of up to five years. 

The study recruited 17,604 participants 45 years or older, with a body mass index over 27, and a history of heart disease but not of diabetes, at 804 clinical sites in 41 countries. Participants were randomly assigned to receive the treatment dose of subcutaneous semaglutide or a placebo and were then monitored for the primary cardiovascular outcome, which was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. A cardiovascular event occurred in 569 of the 8803 patients in the semaglutide group compared to 701 of the 8803 patients in the control group at a mean duration of 39.8 months follow-up. Treatment with semaglutide reduced the risk of this composite measure by 20%. 

It is important to note that a higher percentage of patients discontinued semaglutide than the placebo because of adverse events relating to gastrointestinal symptoms such as nausea, vomiting, and diarrhea. Additionally, higher rates of gallbladder disease were reported in the treatment group compared to placebo, but no significant differences occurred in other serious adverse events. While anti-obesity medications are an essential part of comprehensive obesity care, injectable medications may not be a one-size-fits-all solution to treat obesity due to these side effects. 

While the reduction of cardiovascular events found in the trial was significant and very promising for the future of anti-obesity medications, the SELECT study results are not generalizable to the global population. Only 27.7% of the study participants were women and only 3.3% of the participants were Black. Future research must include more diverse participants, especially racial and ethnic minorities who tend to experience worse outcomes relating to obesity and its comorbidities. 

The implications of the SELECT trial results are far-reaching for obesity treatment and care. As insurance companies debate whether anti-obesity medications are cost-effective, the results from the SELECT trial provide evidence that weight management is an effective strategy to prevent future costly adverse health events, such as cardiovascular diseases.

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