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

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 diabetes.
• •History of type 2 diabetes requiring use of insulin.
• •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.