GLP-1RA Drugs May Reduce Endometrial Cancer Risk When Combined with Progestin Therapy

A recent study suggests that combining glucagon-like peptide 1 receptor agonist (GLP-1RA) drugs, commonly used for type 2 diabetes and weight loss, with progestin therapy may significantly reduce the risk of endometrial cancer in women with benign uterine conditions. The research indicates a substantial decrease in risk compared to hormonal treatment alone.

How GLP-1RAs Impact Endometrial Cancer Risk

The findings, published in JAMA Network Open, demonstrate that women using a combination of GLP-1RAs and progestins experienced a significantly lower incidence of endometrial cancer compared to those treated with progestogens alone. Endometrial cancer is the most prevalent gynecological cancer in developed countries [1].

Progestins are frequently prescribed to address precancerous thickening of the uterine lining or abnormal uterine bleeding. Whereas effective, they don’t address underlying metabolic factors like high blood sugar and insulin resistance, which can contribute to cancer development.

Study Details and Findings

Researchers conducted a retrospective cohort study, analyzing data from the TriNetX database, which contains anonymized electronic medical records from millions of individuals. The analysis included 444,820 women aged 18 years or older with endometrial thickening or other non-cancerous uterine conditions who were prescribed progestogens.

Participants were grouped based on additional treatments: GLP-1RA agonist, metformin (a common diabetes medication), or both. Statistical methods were used to ensure comparable health profiles across groups.

• Reduced Cancer Risk: Patients receiving a GLP-1RA agonist alongside progestins had a 66% lower risk of developing endometrial cancer compared to those treated with progestins alone.
• GLP-1RA Superior to Metformin: The combination of GLP-1RA and progestins proved more effective than combining metformin, and progestins.
• Triple Therapy Benefits: Using all three therapies – GLP-1RA, metformin, and progestins – reduced risk by 63% compared to metformin and progestin therapy, and by 56% compared to progestin monotherapy.
• Lower Hysterectomy Rates: Treatment with GLP-1RA and progestogens was associated with a decreased necessitate for hysterectomy, a common intervention to prevent cancer in these cases. At two years, the risk of hysterectomy was 53% lower, and at five years, it remained 41% lower compared to hormone-only treatment.

GLP-1RAs and Obesity-Related Cancers

GLP-1RAs, such as liraglutide, semaglutide, and tirzepatide, have gained popularity for their effects on weight loss and obesity-related health issues. Recent research suggests these medications may likewise reduce the risk of various obesity-associated cancers, including endometrial cancer [2], [3], [4].

Important Considerations and Future Research

The study authors emphasize that the findings are based on retrospective data analysis and require confirmation through prospective studies and controlled clinical trials. While the addition of a GLP-1RA agonist to progestogen therapy appears linked to a lower risk of endometrial cancer, further research is essential to validate these results.

A clinical trial is currently underway to further investigate the use of GLP-1RAs in conjunction with a levonorgestrel intrauterine device (LNG-IUD) for obese patients with endometrioid intraepithelial neoplasia or grade 1 endometrioid endometrial adenocarcinoma [2].