GLP-1 drugs may reduce uterine fibroid risk for women with type 2 diabetes

Key takeaways:

• Compared with metformin and insulin, GLP-1 receptor agonists may protect against new uterine fibroids in women with type 2 diabetes.
• More research is needed to understand the underlying mechanisms.

DENVER — Women with type 2 diabetes prescribed any GLP-1 receptor agonist were less likely to develop any new-onset uterine fibroids over 5 years compared with those who used metformin or insulin, researchers reported.

Type 2 diabetes and obesity both contribute to insulin resistance, which is associated with increased risk for uterine fibroids, Tina Yi-Jin Hsieh, MD, MPH, a student in the department of biomedical informatics at Harvard Medical School, said during a presentation at the ASRM Scientific Congress & Expo. In January 2020, American Diabetes Association guidelines recommended GLP-1 receptor agonists and SGLT2 inhibitors as first-line agents to lower HbA1c, promote weight loss and provide CV and renal protection for adults with type 2 diabetes, Hsieh said.

“GLP-1 receptor agonists exert many effects across different systems in the human body and also have anti-inflammatory effects to treat a wide variety of diseases,” Hsieh said. “However, the effects of GLP-1 receptor agonists against uterine fibroids — a condition associated with obesity — remain unexplored.”

For the retrospective study, researchers analyzed electronic health records from 30,036 women who initiated GLP-1 receptor agonists therapy compared with 30,036 women who initiated metformin, as well as 30,036 women who initiated GLP-1 receptor agonists compared with 30,036 women who initiated insulin, using data from the TriNetX U.S. Collaborative Network. Researchers used propensity score matching by demographics, comorbidities, BMI, HbA1c and health care utilization for both arms; participants received at least two doses of exclusive GLP-1 receptor agonist therapy, metformin or insulin after a diagnosis of type 2 diabetes. The study period ranged from May 2005 (after the approval of the first GLP-1 receptor agonist) through 2021. Researchers followed patients for 5 years from drug initiation until onset of fibroids, loss to follow-up or September 2024, whichever came first.

Researchers found women who received at least two doses of a GLP-1 receptor agonist had a 27% lower risk for developing any new-onset fibroids compared with metformin users (RR = 0.73; 95% CI, 0.66-0.81), with similar results in analyses stratified by fibroid type. Researchers observed greater protection against new-onset fibroids for women who received at least six doses of any GLP-1 receptor agonist (RR = 0.65; 95% CI, 0.56-0.76).

Women who used a GLP-1 receptor agonist similarly has a 23% lower risk for fibroids compared with insulin users (HR = 0.77; 95% CI, 0.69-0.85).

Hsieh noted that there was no detailed information available about fibroid size, severity or symptoms; between 82% and 85% of lesion locations were coded as “unspecified.” The sample size was not large enough to compare differences by race.

“In women with type 2 diabetes, GLP-1 receptor agonists may protect against new-onset uterine fibroids compared to both metformin and insulin,” Hsieh said. “We recommend further research, including prospective cohorts and basic research, to understand the underlying therapeutic mechanisms.”