Overview
- The randomized trial enrolled adults 45 and older with established cardiovascular disease and no diabetes across 41 countries, comparing weekly 2.4 mg semaglutide with placebo.
- Risk reductions were consistent from a BMI of 27 through severe obesity and were not predicted by how much weight participants lost early in treatment.
- Mediation analysis estimated about 33% of the effect was explained by decreases in waist circumference, a proxy for visceral fat.
- Investigators cite potential pathways such as improved endothelial function, reduced inflammation, better blood pressure control and lipid changes, which require confirmation.
- Authors argue BMI-based restrictions on access should be revisited and, noting demographic limits and Novo Nordisk funding, call for more diverse, longer-term safety studies.