Clinical Research Directory

Inclusion 1. Age ≥ 18 years 2. Histologically confirmed endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid EC 3. BMI ≥ 30 kg/m2 4. Presence of at least one obesity-associated metabolic comorbidity, including: a. Hypertension defined as: i. Documented diagnosis of hypertension, regardless of treatment status, documented in the medical records, or ii. Participants receiving antihypertensive therapy, or iii. BP ≥ 130/80 mmHg over 3 independent measurements, or iv. Single BP ≥ 160/100 mmHg b. Hyperlipidemia defined as: i. Documented diagnosis of hyperlipidemia, regardless of treatment status, documented in the medical record, or ii. Participants receiving lipid-lowering therapy, or iii. Triglycerides \> 200 mg/dL, or iv. LDL Cholesterol \> 130 mg/dL c. Type 2 Diabetes defined as: i. Documented diagnosis of Type 2 diabetes mellitus, regardless of treatment status, documented in the medical record, or ii. Receiving glucose-lowering therapy, or iii. Impaired glucose tolerance (Hgb A1c \> 6.0%) d. Diagnosed with sleep apnea 5. For participants diagnosed with grade 1 endometrioid endometrial carcinoma: clinical stage 1A disease with MRI-confirmed myometrial invasion \< 50% and no evidence of metastatic disease 6. For participants with EIN: no evidence of extrauterine disease based on clinically appropriate evaluation 7. Ability to provide informed consent and comply with study procedures and follow-up Exclusion 1. Mismatch repair-deficient (MMRd) tumors 2. p53-abnormal tumors 3. Known hypersensitivity or contraindication to either: 1. Tirzepatide, or 2. LNG-IUD 4. Prior LNG-IUD in place at the time of EIN or endometrial cancer diagnosis 5. Current systemic progestin therapy 6. Current treatment with tirzepatide or another GLP-1 receptor agonist/GLP-1-GIP receptor agonist, or prior treatment with these agents within 1 month before study enrollment 7. Type 1 diabetes or a history of pancreatitis, medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2 (MEN2) 8. Pregnancy, breastfeeding, or intention to become pregnant during the study treatment 9. Concurrent malignancy requiring active treatment (except non-melanoma skin cancer) 10. Any medical, psychiatric, or social condition, that in the opinion of the investigator, would interfere with study participation or safety 11. Participants with diabetic eye disease, including non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema 12. Severe renal impairment, defined as eGFR \< 30 mL/min/1.73m2