Combining a weight loss drug with an IUD for women with obesity and endometrial hyperplasia

Primary Prevention and Uterine Preservation in Premenopausal Women With Obesity and Endometrial Hyperplasia

This study is testing if combining a weight loss drug with an IUD can help women with obesity and endometrial hyperplasia keep their uterus while also losing weight and improving their quality of life.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 96 (estimated)
• Ages: 18 Years to 45 Years
• Sex: Female
• Sponsor: Washington University School of Medicine (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 1 site (Saint Louis, Missouri)
• Trial ID: NCT05829460 on ClinicalTrials.gov

What this trial studies

This clinical trial investigates the effectiveness of combining the GLP-1R agonist semaglutide with a levonorgestrel intrauterine device (LNG-IUD) in premenopausal women suffering from endometrial hyperplasia who wish to preserve their uterus. The study aims to determine if this combination leads to better outcomes in uterine preservation, weight loss, and overall quality of life compared to using the LNG-IUD alone. Participants will be monitored for their endometrial and metabolic responses to the treatment. The trial includes a telemedicine behavioral weight program to support participants in achieving weight loss goals.

Who should consider this trial

Good fit: Ideal candidates are premenopausal women aged 18 to 45 with a diagnosis of complex atypical endometrial hyperplasia and a body mass index (BMI) of 30 kg/m2 or higher.

Not a fit: Patients who are not premenopausal, have a BMI below 30 kg/m2, or do not wish to preserve their uterus may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a new option for women with endometrial hyperplasia to preserve their uterus while managing obesity and improving their quality of life.

How similar studies have performed: While the combination of GLP-1R agonists and progestin therapy is a novel approach, similar studies have shown promise in managing obesity and endometrial conditions, indicating potential for success.

Eligibility criteria

Inclusion Criteria:

* Diagnosis of histologically confirmed complex atypical endometrial hyperplasia.

  * Patients with a previous diagnosis of AEH who are already being followed with conservative management with oral or LNG-IUD progestin therapy are eligible provided they have not previously been on a GLP-1R agonist within 3 months prior to enrollment.
  * For patients with a previous diagnosis of AEH who have been placed on progestin prior to study entry, the duration of IUD or oral progestin use prior to trial entry should be less than or equal to 6 months.
* Premenopausal woman with a uterus.
* At least 18 years of age and no more than 45 years of age.
* Interested in uterine preservation/fertility-sparing treatment.
* BMI ≥ 30 kg/m2.
* Prior or current receipt of progestin is allowed as above. Willingness to undergo placement of LNG-IUD at the time of study entry.
* Prior or current receipt of metformin is allowed.
* Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

* Prior use of GLP-1 receptor agonist (exenatide, liraglutide, or other) or pramlintide or any DPP-4 inhibitor in the 3 months prior to date of registration.
* History of type 1 or type 2 diabetes, and/or the following biochemical indications: fasting plasma glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%, two-hour plasma glucose ≥ 200 mg/dL during an oral glucose tolerance test (OGTT), or random glucose ≥ 200 mg/dL in the presence of symptoms
* Acute decompensation of glycemic control.
* Concomitant use of other weight management drugs or drugs for short-term weight loss.
* History of surgery or use of a device to treat obesity.
* Uncontrolled thyroid disease
* Acute coronary or cerebrovascular event in the previous 60 days.
* Currently planned coronary, carotid, or peripheral artery revascularization.
* Chronic heart failure (NYHA class IV).
* Evidence of renal dysfunction as defined by creatinine clearance \< 60 ml/minute.
* History of solid organ transplant or awaiting solid organ transplant.
* Diagnosis of any malignant neoplasm or current, active treatment with chemotherapy or radiation.
* Family or personal history of multiple endocrine neoplasia syndrome type 2 (MEN 2) or familial medullary thyroid carcinoma (MTC).
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to progestin, semaglutide, or other agents used in the study.
* History of diabetic retinopathy.
* Recent history of pancreatitis, defined as less than 6 months prior to enrollment.
* History of suicidal attempts or active suicidal ideation.
* Significant active psychiatric disease, including recent psychiatric inpatient admission or use of any psychiatric medications that are not stabilized.
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
* Pregnant and/or breastfeeding. Participants must have a negative serum pregnancy test within 7 days of date of registration.
* Patients with HIV are eligible unless their CD4+ T-cell counts are \< 350 cells/mcL, they have a history of AIDS-defining opportunistic infection within the 12 months prior to registration, or they are receiving anti-retrovirals that affect progestin levels. Concurrent treatment with effective ART according to DHHS treatment guidelines is recommended.

Where this trial is running

Saint Louis, Missouri

• Washington University School of Medicine — Saint Louis, Missouri, United States (Recruiting)

Study contacts

• Principal investigator: Andrea R Hagemann, M.D., MSCI — Washington University School of Medicine
• Study coordinator: Andrea R Hagemann, M.D., MSCI

Conditions Endometrial Hyperplasia