New analyses from the SELECT trial, the longest clinical trial of Wegovy (semaglutide) to date, reveal sustained weight loss and potential heart benefits that extend beyond weight reduction. The study, which followed over 17,600 participants for up to four years, was presented at the European Congress on Obesity and published in Nature Medicine.
Sustained Weight Loss Over Four Years
The SELECT trial demonstrated that participants taking semaglutide, the active ingredient in Wegovy, experienced an average weight loss of just over 10% compared to a 1.5% loss in the placebo group. Notably, weight loss continued for approximately 65 weeks before plateauing, and this reduction was sustained for the entire four-year duration of the study.
Cardiovascular Benefits Independent of Weight Loss
Initial results from the SELECT trial showed a 20% reduction in the risk of heart attack, stroke, or heart-related death in individuals with existing cardiovascular risk who were either obese or overweight. Further analysis suggests that these cardiovascular benefits may not be solely attributable to weight loss. The reduction in major adverse cardiovascular events was similar in participants who lost 5% or more of their body weight and those who lost less or even gained weight.
Dr. John Deanfield of University College London noted, "This suggests alternative mechanisms of improved cardiovascular outcome beyond reduction in adiposity."
Safety Profile
The safety profile of Wegovy remained consistent with previous trials. While more participants in the Wegovy group discontinued the trial due to side effects (17% vs. 8% in the placebo group), these were primarily known gastrointestinal issues such as nausea, diarrhea, vomiting, and constipation. There were no new safety signals identified. Gallbladder disorders, such as gallstones, were observed slightly more frequently in the Wegovy group (2.8%) compared to the placebo group (2.3%).
Implications for Treatment and Coverage
The findings from the SELECT trial have significant implications for the treatment of obesity and cardiovascular disease. Dr. Daniel Drucker, a GLP-1 research pioneer at the University of Toronto, suggests that semaglutide and similar medicines may offer cardio-protective effects independent of weight loss. This raises the possibility of using these drugs to prevent cardiovascular events in individuals who may not be obese or overweight but have a history of heart attack or stroke.
Furthermore, experts argue that the SELECT trial results should prompt a re-evaluation of insurance coverage criteria for Wegovy. The potential for heart-health benefits, even without significant weight loss, suggests that broader coverage may be warranted to improve health outcomes and reduce healthcare costs.
