Semaglutide Shows Promise in Cardiovascular Risk Reduction

Semaglutide, a medication originally meant to treat type 2 diabetes, was shown in a major study in Philadelphia, Pennsylvania, to significantly decrease cardiovascular events in people with overweight or obesity and past CVD who are not diabetic. Participants in the study at 804 sites in 41 countries showed a 1.5% reduced incidence of major adverse cardiovascular events (MACE) than those who received a placebo.  

Dr. A. Michael Lincoff of the Cleveland Clinic stated at the American Heart Association 2023 Scientific Sessions that semaglutide is the first weight management drug to be demonstrated to minimize the risk of cardiovascular events in a thorough randomized controlled study. The knowledge that being overweight and obese are avoidable causes of cardiovascular disease has resulted in significant advances in the profession.  

Despite the good findings, the study found that the semaglutide group had a greater chance of permanent treatment cessation due to GI adverse effects (16.6% vs. 8.2%). Cynthia Jackevicius, a pharmacist at Western University of Health Sciences, expressed worry that the high monthly cost of semaglutide (about $1,300) would discourage its broad usage and add to existing healthcare inequities.  

Dr. Martha Gulati, president of the American Society of Preventive Cardiology, emphasized the importance of regulatory approval for this new indication, expressing confidence that the recently approved tirzepatide (Zepbound; Eli Lilly) will improve availability and lower prices.  

The SELECT study included 45-year-olds with established CVD, a BMI of at least 27 kg/m2, and no history of diabetes. Semaglutide was connected to fewer cases of heart failure, mortality from any cause, coronary revascularization, and the start of diabetes, in addition to decreasing the incidence of MACE. Individuals using semaglutide lost more weight and had higher reductions in a variety of cardiometabolic risk variables.  

Although the risk of MACE decreased early in the experiment, before significant weight loss was accomplished, the mechanism behind this cardiovascular advantage remains unknown. Direct effects on inflammation, endothelial function, and other factors, as well as the indirect effects of weight loss, have generated debate in light of the findings.  

Given that over a billion people worldwide will be obese by 2030, the results of the SELECT experiment are critical. According to Dr. Ania Jastreboff of Yale School of Medicine, treating obesity with effective drugs like GLP-1 receptor agonists would result in a paradigm shift, foreseeing a future in which doctors would focus on obesity to alleviate illnesses like hypertension, hyperlipidemia, and type 2 diabetes.  

Despite the many accomplishments, there was a lack of ethnic and cultural diversity in the trial groups, which was a key shortcoming in the SELECT research. The underrepresentation of women and people of color highlights the importance of improved inclusion in future studies to ensure that all patients who require these drugs receive them.  

Finally, the SELECT research has been acknowledged as a watershed moment in the obesity struggle, spurring a call to action to tackle the epidemic by treating obesity as the complicated, chronic disease that it is. The findings represent a paradigm shift in the way obesity is addressed, implying that interventions such as medications, in addition to lifestyle changes, might significantly improve health outcomes in individuals with cardiovascular disease.  

Journal Reference  

Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., … Ryan, D. H. (2023). New England Journal of Medicine. doi:10.1056/nejmoa2307563