Semaglutide Reduces Cardiovascular Risk Regardless of Weight Loss, Study Finds

New research indicates that semaglutide, a medication commonly used for weight management, delivers significant cardiovascular benefits that extend beyond its effects on body weight. The findings, published in a leading medical journal, reveal that semaglutide lowers the risk of serious cardiovascular events in individuals with obesity, even when weight reduction is less than five percent within the first 20 weeks of treatment.

The study analyzed data from a large, randomized, controlled Phase III clinical trial involving 17,604 participants aged 45 and older from 41 countries. All participants had a body mass index (BMI) of 27 or higher and a history of atherosclerotic cardiovascular disease, such as previous heart attack, stroke, or symptomatic peripheral arterial disease. Notably, individuals with diabetes were excluded from the trial to focus specifically on the impact of semaglutide in non-diabetic patients with established cardiovascular risk.

Participants were randomly assigned to receive either 2.4 mg of semaglutide administered subcutaneously once weekly or a placebo. The medication dose was gradually increased over a 16-week period to reach the target dose. The primary endpoint of the trial was the time to the first occurrence of a major adverse cardiovascular event (MACE), including cardiovascular death, nonfatal heart attack, or nonfatal stroke. Body weight and waist circumference were measured periodically throughout the study, with a median follow-up period of approximately 40 months.

Results demonstrated that semaglutide consistently reduced the incidence of major cardiovascular events compared to placebo, regardless of the degree of weight loss achieved by week 20. The overall risk reduction was approximately 20 percent across all obesity subgroups. Higher baseline body weight or waist circumference was associated with an elevated risk of cardiovascular events; however, semaglutide's protective effects were observed consistently, independent of these initial measurements.

The analysis further showed that for every five kilograms of weight lost or five centimeters reduction in waist circumference, the risk of a major cardiovascular event decreased by about four percent. This relationship was particularly pronounced for waist circumference in the placebo group, while the effect on baseline weight was less evident. Importantly, the cardiovascular risk reduction with semaglutide was maintained even in participants who experienced minimal weight loss, underscoring the drug's direct benefits on heart health beyond its role in weight management.

The study's findings suggest that the mechanism by which semaglutide reduces cardiovascular risk may involve metabolic and vascular effects not solely attributable to weight loss. Researchers emphasize that semaglutide could play a crucial role in the prevention of serious cardiovascular events among individuals with obesity and established heart disease, regardless of their weight loss outcomes.

These results support the broader use of GLP-1 receptor agonists like semaglutide for cardiovascular risk reduction in this high-risk population. Healthcare professionals may consider semaglutide as part of a comprehensive approach to managing cardiovascular health in patients with obesity, alongside lifestyle modification and other medical therapies. Ongoing research will be essential to further clarify the underlying mechanisms and to optimize patient selection for this therapeutic strategy.