GLP-1 Drugs Tied to Reduced Risk of Uterine Fibroids

DENVER — In women with type 2 diabetes, use of GLP-1 receptor agonists was associated with a reduced risk of new-onset uterine fibroids compared with other antidiabetic agents, a retrospective cohort study suggested.

Among patients who took at least two doses of medication, GLP-1 receptor agonists were associated with a significantly lower risk of new-onset uterine fibroids compared with metformin (risk ratio [RR] 0.73, 95% CI 0.66-0.81) and insulin (RR 0.75, 95% CI 0.69-0.81), reported Tina Yi Jin Hsieh, MD, MPH, of Harvard Medical School in Boston.

In a sensitivity analysis, similar effects were seen with six or more doses of GLP-1 drugs compared with metformin (RR 0.65, 95% CI 0.56-0.76) and insulin (RR 0.76, 95% CI 0.68-0.84), Hsieh noted during a presentation at the American Society for Reproductive Medicine annual meeting.

Type 2 diabetes and obesity contribute to insulin resistance, which is linked to an increased risk of uterine fibroids. Prescriptions for GLP-1 receptor agonists have skyrocketed since 2020, in part for their weight-loss effects. Research has shown many beneficial effects with GLP-1 receptor agonists, but this study is the first to assess their effects on uterine fibroids.

Hsieh said that prospective research is still needed to understand the underlying mechanism.

Susanna Mitro, PhD, a research scientist at Kaiser Permanente Northern California in Oakland, who also researches fibroids, told MedPage Today that with the increased usage of GLP-1 receptor agonists, this study looks at an important question.

“This is the first study I’ve seen that has investigated this question specifically, but I do think it is a natural extension of the literature that we’ve seen that diabetes is protective, potentially, for fibroids,” she said.

Mitro pointed out that the average age of participants in this study was on the older end — 59 — which impacts how the results should be interpreted. She said it is rare for postmenopausal women to “be diagnosed with fibroids and have it be a true diagnosis, as opposed to some other sort of something going on with the uterus.”

Thus, “it’ll be interesting to see, especially among younger patients, whether we see the same associations,” she added.

Hsieh told MedPage Today that she plans to stratify her results by menopausal status.

For this study, Hsieh and team used the TriNetX database, which includes electronic health records from 95 large healthcare organizations caring for more than 200 million patients across the U.S. This study cohort included women who had at least two doses of a GLP-1 receptor agonist, metformin, or insulin after their type 2 diabetes diagnosis from January 2005 through December 2021.

The researchers followed participants for 5 years from drug initiation until the onset of fibroids, loss to follow-up, or Sept. 1, 2024 — whichever came first. Women with type 1 diabetes or those who had undergone a hysterectomy were excluded.

Among the groups, body mass index (BMI), HbA1c levels, healthcare utilization rates, and hypertensive disease rates were similar; 63% of participants were white, 20% were Black, 4% were Asian, and 11% were of Hispanic ethnicity.

Hsieh noted a few limitations to the study, including residual confounding and not having a big enough sample size to analyze racial differences. Additionally, the researchers didn’t have granular information about fibroid size, severity, or symptoms, and they weren’t able to incorporate weight/BMI changes or HbA1c changes as variables in their analysis.

She also noted that they cut off their study time period in 2021 to mitigate confounding from the GLP-1 receptor agonist shortage in 2022.

In the future, Hsieh said that she and her team are interested in looking at other antidiabetic medications and a composite outcome with heavy menstrual bleeding, and investigating the effects of GLP-1 receptor agonists on patients after the onset of fibroids.

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