A major trial has shown that the weight-loss drug Wegovy reduces cardiovascular risks independently of weight loss. The benefits apply even to those with mild obesity. Researchers analyzed data from over 17,000 participants to reach this conclusion.
The SELECT trial, involving 17,604 people aged 45 and older who were overweight or obese with established heart disease but no diabetes, compared semaglutide—the active ingredient in Wegovy and Ozempic—against a placebo. In November 2023, initial results indicated that semaglutide reduced the risk of heart attacks, strokes, or other major cardiac events by 20 percent over approximately two years.
Further analysis revealed these heart health improvements were not solely due to weight loss. Participants with a starting body mass index (BMI) of 27—indicating mild obesity—experienced similar cardiovascular benefits as those with BMIs up to 44, severe obesity. The amount of weight lost, whether in the first 20 weeks or over the full trial duration, had little impact on the outcomes.
Abdominal fat played a partial role: a smaller waist circumference at the study's start correlated with lower cardiovascular risks in both groups. On semaglutide, each 5-centimeter reduction in waist size was linked to about a 9 percent lower risk of events, accounting for roughly one-third of the drug's protective effect. The remaining benefits remain unclear but may involve direct actions on the heart.
In the placebo group, weight loss was associated with a slightly increased risk of heart problems, possibly reflecting underlying health issues, according to John Deanfield at University College London. "The take-home message is that the benefit of these drugs for your heart and arteries is not dependent on your weight loss, which reframes these drugs as being disease-modifying drugs independent of weight benefit," Deanfield said.
Potential mechanisms include improved blood vessel linings, blood pressure regulation, anti-inflammatory effects, and targeting of epicardial adipose tissue around the heart, as suggested by experts like Gianluca Iacobellis at the University of Miami. Further research is needed to identify optimal candidates for these drugs, noted Stefano Masi at the University of Pisa.
The findings, published in The Lancet (DOI: 10.1016/S0140-6736(25)01375-3), highlight semaglutide's broader potential beyond weight management and diabetes treatment.