Study finds popular weight-loss drug may also treat lymphatic disease common among cancer survivors

The lymphatic system is the body’s drainage system: It collects excess fluids from tissue, which then flow into the bloodstream. When the lymphatic system is not draining properly, there’s a risk of lymphedema, a chronic and debilitating disease that commonly causes swelling in limbs and for which there is no approved drug therapy.  

A study from Tulane University, however, has found that a popular weight-loss drug may help the body’s lymphatic system drain more effectively.  

The research, published in the journal Microcirculation, found that semaglutide — one of a group of medications commonly known as GLP-1s — could widen vessels within the lymphatic system, allowing the vessels to move larger quantities of fluid with each contraction. The study could offer insight into how GLP-1s might one day treat lymphedema.  

Lymphedema affects more than 250 million people worldwide. In the U.S., the most common form of the disease, secondary lymphedema, predominantly affects cancer survivors, who can develop the disease after treatment, as well as those with obesity.  

The study was the first to identify GLP-1 receptors in lymphatic vessels.  

“If our findings are validated by ongoing clinical studies, the use of GLP-1 receptor agonists (which activate receptors) would represent one of the first therapeutic alternatives for secondary lymphedema patients,” said lead study investigator Jorge A. Castorena, associate professor in the School of Medicine and a member of the Tulane Cancer Center. “In the specific case of cancer-related lymphedema, I envision these drugs not only being used to treat lymphedema, but also to reduce the risk of developing this disease in the first place, if given before or immediately after an intervention for cancer.”

In the study, semaglutide improved the pumping capacity of lymphatic vessels in healthy mice and in mouse models of obesity and metabolic disease. In one key experiment, a single low dose increased the volume of fluid moved with each contraction by about 25%. The drug also improved the vessels’ ability to propel fluid against pressure, a function that is especially important in parts of the body where fluid must move upward against gravity.  

Researchers, including lead author Mary E. Schulz, a doctoral student at Tulane School of Medicine, also found that semaglutide improved or restored impaired pumping function in lymphatic vessels from mice with obesity-related and cholesterol-related dysfunction. That suggests the drug may do more than support weight loss alone and could have a direct effect on the lymphatic system itself.  

The study adds laboratory evidence to recent clinical observations linking GLP-1 drugs to improvements in lymphedema. The authors cited earlier reports suggesting these drugs may reduce the risk of cancer-related lymphedema or improve symptoms in some patients, though they emphasized that more research is needed.  

Castorena noted that while this work remains preclinical, preliminary reports from another ongoing study are encouraging. Led by one of Castorena's co-authors, Joseph Dayan of The Institute for Advanced Reconstruction, the study showed a decrease in swelling of around 10% in a group of lymphedema patients after they received the lowest prescribed dosage of semaglutide for only three months.  

“This is really an exciting time in the lymphatic field as secondary lymphedema patients will soon have therapeutic alternatives,” Castorena said.