Minneapolis, April 25: Glucagon-like peptide-1 receptor agonists, known as GLP-1 drugs, are highly effective at helping people lose weight and substantially lower the risk of heart attacks, strokes and death from heart disease. A new study conducted in mice suggests that the drugs’ effect on how blood vessels respond to insulin may be a key driver of this cardiovascular benefit in those with obesity. Researchers will present their work this week at the 2026 American Physiology Summit in Minneapolis. The Summit is the flagship annual meeting of the American Physiological Society (APS).
“I believe the increased vascular relaxation to insulin found in mice may be one of the reasons why humans on GLP-1 drugs have cardiovascular protection,” said the study’s first author Augustine L. Udefa, MSc, a PhD candidate at the University of Missouri-Columbia.
In a healthy body, insulin clears sugar from the blood and also signals the blood vessels to relax, ensuring blood and nutrients flow easily to our organs. In someone with obesity, the body becomes less sensitive to insulin and blood vessels become stiff, leading to high blood pressure and poor circulation. Losing weight can help to counteract this, but vascular relaxation is what actually prevents heart attacks and other heart problems.
The researchers wanted to study how GLP-1 drugs affect vascular relaxation directly, in addition to helping with weight loss. To do this, they raised mice on a high-fat, high-sugar diet, causing them to become obese. Half of the mice received injections of semaglutide, a GLP-1 drug, starting at 20 weeks of age (equivalent to early middle age in humans), while the others received a control injection.
After eight weeks, the mice receiving semaglutide showed significant improvements in insulin-induced relaxation in blood vessels. These mice also were leaner and had improved glucose tolerance and reduced mean arterial pressure, all indicators of improved cardiometabolic health.
The findings suggest that semaglutide helps blood vessels relax properly again when insulin is present, which enhances the overall function and sensitivity of the arteries. This may help explain why the cardiovascular benefits of GLP-1 drugs often exceed what would be expected from weight loss alone, according to researchers.
The researchers next plan to investigate the specific mechanisms by which semaglutide helps blood vessels relax and stay healthy.
