A prespecified analysis of the SELECT trial reports that weekly semaglutide lowered the risk of heart attacks and strokes by about 20% in adults with established cardiovascular disease and overweight or obesity—even when little weight was lost—suggesting benefits beyond slimming alone.
The new analysis, published in The Lancet and led by researchers at University College London, examined data from 17,604 adults aged 45 and older with overweight or obesity (BMI ≥27) and established cardiovascular disease, but without diabetes. Participants across 41 countries were randomly assigned to once‑weekly semaglutide or placebo. Earlier results from the same trial showed a 20% reduction in major adverse cardiovascular events (MACE) with semaglutide. (ucl.ac.uk)
In this prespecified analysis, the magnitude of cardiovascular risk reduction was consistent across baseline body sizes, including among people with BMI as low as 27. The benefit also did not depend on how much weight participants lost during the first 20 weeks of treatment. However, a reduction in waist circumference—an indicator of abdominal fat—statistically explained roughly one‑third of the observed protection over about two years, pointing to additional mechanisms beyond weight change. (ucl.ac.uk)
Professor John Deanfield of UCL’s Institute of Cardiovascular Science said: “Abdominal fat is more dangerous for our cardiovascular health than overall weight and therefore it is not surprising to see a link between reduction in waist size and cardiovascular benefit. However, this still leaves two thirds of the heart benefits of semaglutide unexplained.” He added: “These findings reframe what we think this medication is doing. It is labelled as a weight loss jab but its benefits for the heart are not directly related to the amount of weight lost. In fact it is a drug that directly affects heart disease and other diseases of ageing.” (ucl.ac.uk)
The authors suggest that semaglutide’s cardioprotective effects may involve improvements in endothelial function, reduced inflammation, better blood‑pressure control, and lower lipid levels. While the analysis focused on semaglutide, they note the mechanisms could extend to other GLP‑1 receptor agonists. Semaglutide, a GLP‑1 receptor agonist that mimics incretin hormones to help regulate blood sugar, was first approved for type 2 diabetes and later for chronic weight management. (ucl.ac.uk)
Regulatory context in the UK has evolved alongside these findings. In July 2024, the Medicines and Healthcare products Regulatory Agency approved a new indication for Wegovy (semaglutide 2.4 mg) to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and overweight or obesity (BMI ≥27). On the NHS, Wegovy remains available for weight management via specialist services under NICE guidance. (gov.uk)
The SELECT trial’s earlier primary results—6.5% MACE with semaglutide versus 8.0% with placebo over a mean of about 40 months—support the headline 20% relative risk reduction cited in the new analysis. The Lancet paper was funded by Novo Nordisk, the drug’s manufacturer. (acc.org)
The researchers emphasize that the trial cohort was predominantly male and white and call for future studies to include more diverse populations to clarify whether benefits are consistent across sex and ethnicity. (ucl.ac.uk)
