Tirzepatide and Levonorgestrel IUD Therapy for EIN and Early-Stage Endometrial Cancer

A regiszterben nem jelölt feltételek

• Inclusion
• Age ≥ 18 years
• Histologically confirmed endometrial intraepithelial neoplasia (EIN) or grade 1 endometrioid EC
• BMI ≥ 30 kg/m2
• Presence of at least one obesity-associated metabolic comorbidity, including:
  • 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
• 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
• For participants with EIN: no evidence of extrauterine disease based on clinically appropriate evaluation
• Ability to provide informed consent and comply with study procedures and follow-up
  • Exclusion
• Mismatch repair-deficient (MMRd) tumors
• p53-abnormal tumors
• Known hypersensitivity or contraindication to either:
  • Tirzepatide, or
  • LNG-IUD
• Prior LNG-IUD in place at the time of EIN or endometrial cancer diagnosis
• Current systemic progestin therapy
• 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
• Type 1 diabetes or a history of pancreatitis, medullary thyroid carcinoma, or Multiple Endocrine Neoplasia syndrome type 2 (MEN2)
• Pregnancy, breastfeeding, or intention to become pregnant during the study treatment
• Concurrent malignancy requiring active treatment (except non-melanoma skin cancer)
• Any medical, psychiatric, or social condition, that in the opinion of the investigator, would interfere with study participation or safety
• Participants with diabetic eye disease, including non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy, or diabetic macular edema
• Severe renal impairment, defined as eGFR < 30 mL/min/1.73m2