Adding glucagon-like peptide-1 (GLP-1) receptor agonists (such as Ozempic) to progestin hormone therapy significantly reduces the risk of endometrial cancer. This conclusion was reached by researchers from the Texas Tech University Health Sciences Center in El Paso. The findings were published in JAMA Network Open.

Endometrial cancer is the most common gynecologic cancer in developed countries. Progestins are used to treat precancerous changes of the uterine lining and abnormal uterine bleeding; however, they do not eliminate metabolic risk factors — such as hyperglycemia and insulin resistance — which may contribute to tumor development.

The researchers conducted a retrospective analysis using data from the TriNetX database, which contains anonymized electronic medical records. The study included 444,820 women over the age of 18 with endometrial thickening or other benign uterine conditions who were receiving progestin therapy. Participants were divided into groups depending on whether they were taking GLP-1 receptor agonists, metformin, or a combination of both.

The results showed that women who received GLP-1 receptor agonists together with progestins had a 66% lower risk of developing endometrial cancer compared with patients treated with progestins alone. The combination proved more effective than regimens including metformin. Triple therapy (GLP-1 receptor agonists, metformin, and progestins) reduced risk by 63% compared with dual therapy and by 56% compared with progestin monotherapy.

In addition, combination treatment was associated with a reduced need for hysterectomy. After two years, the risk of surgical removal of the uterus among patients receiving GLP-1 receptor agonists together with progestins was 53% lower. After five years, the rate remained 41% lower compared with the group receiving hormone therapy alone.

The authors note that the findings are based on a retrospective analysis of medical records and therefore cannot directly establish a causal relationship. Nevertheless, the results suggest a potential benefit of targeting metabolic disorders — particularly insulin resistance and elevated glucose levels — as an additional strategy for preventing endometrial cancer in women at increased risk.