Glucagon-like peptide-1 receptor agonists may reduce endometrial cancer risk in endometrial hyperplasia

1. Glucagon-like peptide-1 receptor agonists (GLP-1RA) in combination with progestins are significantly more effective at reducing endometrial cancer (EC) risk compared to progestins alone in female patients with endometrial hyperplasia or other nonmalignant uterine conditions.

Evidence Rating Level: 2 (Good)

Among patients with abnormal uterine bleeding (AUB), the presence of metabolic conditions (e.g. obesity, insulin resistance, type 2 diabetes mellitus (T2DM)) increases the risk of EC. Progestin therapy remains the therapy of nonsurgical management of AUB. However, given the role of metabolic factors in endometrial proliferation and carcinogenesis, patients may benefit from pharmacotherapy that targets these factors. GLP-1RAs have been approved for weight loss and T2DM; emerging evidence suggests they may also have antitumorigenic properties. This retrospective cohort study evaluated whether GLP-1RA in combination with progestin therapy is associated with a reduced risk of developing EC among women with endometrial hyperplasia (EH) or other benign uterine pathologies. Female patients aged 18 years or older who were diagnosed with EH or benign uterine pathology and received progestin were included (n = 444 820; mean [SD] age, 35.5 [11.0] years). 18 414 patients received GLP-1RA combined with progestins (mean [SD] age, 43.1 [10.2] years). Patients receiving GLP-1RA and progestins had a significantly lower risk of EC than those receiving progestin alone (HR, 0.34 [95% CI, 0.27-0.44]) or progestin and metformin (HR, 0.30 [95% CI, 0.15-0.59]). Triple therapy with GLP-1RA, metformin, and progestin was more effective at reducing EC risk than metformin and progestin (HR, 0.37 [95% CI, 0.25-0.53]). Future randomized controlled trials are required to further establish this relationship.

Click here to read this study in JAMA Network Open

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