A study found that semaglutide, the active ingredient in the obesity drug Wegovy, lowers the risk of cardiovascular disease. It did not matter even if weight did not drop. The cardiovascular benefit was the same for people who were not obese or who failed to lose weight.
Researchers led by Professor John Deanfield of University College London (UCL) said in the international journal Lancet on the 22nd (local time), "For every 5 centimeters reduction in waist circumference after administering semaglutide, the risk of cardiovascular disease decreases by an average of 4%."
Semaglutide is a drug that mimics the glucagon-like peptide-1 (GLP-1) hormone. GLP-1 is secreted from the small intestine after meals. It promotes the secretion of insulin from the pancreas, which lowers blood sugar, and suppresses glucagon, which raises blood sugar. In the brain, it suppresses appetite and slows the rate at which food leaves the stomach, increasing satiety.
The researchers conducted an experiment on 17,604 overweight or obese adults aged 45 or older with a body mass index (BMI—the value obtained by dividing weight by height squared) above 27. None had diabetes, but all had cardiovascular issues. They injected semaglutide into the thigh or abdomen at home once a week. The dose started at 0.24 mg and gradually increased to 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg.
Previously, in 2023, the researchers reported that semaglutide reduced the risk of heart attack, stroke, or other heart diseases by 20%. This time, to determine whether the effect came from weight loss, the team conducted an in-depth analysis of the clinical trial data.
As a result, the risk of cardiovascular disease fell similarly whether the body mass index was 27 or 44. In other words, whether moderately overweight or severely obese, the risk of cardiovascular disease decreased for all. The researchers explained that weight loss during the first 20 weeks of the trial did not have a particular impact on cardiovascular outcomes.
Abdominal fat was linked to cardiovascular disease. As waist circumference decreased, the risk of cardiovascular disease also declined. The researchers said, "Visceral fat in the abdomen is more harmful to the cardiovascular system than peripheral fat (under the skin)."
Sonya Babu-Narayan, clinical director at the British Heart Foundation, told the Science Media Centre, "Beyond reductions in weight or fat, more research is needed to identify other mechanisms of cardiovascular benefit such as improved vascular health, blood pressure and blood sugar control, or inflammation." The UCL team also said, "A limitation is that the study population was predominantly white men."
Tim Chico, a professor at the University of Sheffield, said, "Adding semaglutide to drugs commonly taken by people with heart disease, such as aspirin and statins, is likely to be beneficial," but added, "Medication alone is not enough; a healthy diet, physical activity, and smoking cessation are needed."
References
Lancet (2025), DOI: https://doi.org/10.1016/S0140-6736(25)01375-3