Effect of Tirzepatide Plus Intensive Lifestyle Therapy on Body Weight and Metabolic Health in Latinos With Obesity (TRZ)

Inclusion Criteria: Self-reported Hispanic and/or Latino heritage Body Mass Index (BMI) 30-42 kg/m² HbA1c ≤ 6.4% Exclusion Criteria: Previous diagnosis of diabetes or fasting glucose ≥ 126 mg/dl or 2 hr oral glucose tolerance test plasma glucose ≥ 200 mg/dl Unstable weight (≥4% during the last 2 months prior to study enrollment) CPAP treatment for obstructive sleep apnea Severe cardiovascular disease within the 6 months prior to study enrollment Severe organ system dysfunction Known clinically significant gastric emptying abnormality History of chronic or acute pancreatitis Thyroid-stimulating hormone (TSH) >1.5X the upper limit of normal Medical conditions that cause obesity History of significantly active or unstable Major Depressive Disorder or other severe psychiatric disorder within the last 2 months Active substance abuse with alcohol or drugs Uncontrolled hypertension Liver disease Calcitonin level of ≥20 ng/L if eGFR ≥60 mL/min/1.73 m2 or ≥35 ng/L if eGFR <60 mL/min/1.73 m2 Family or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 History of active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous cell skin cancer, in situ carcinomas of the cervix, or in situ prostate cancer) for less than 5 years Severe anemia Pregnant or breastfeeding Metal implants that preclude MRI testing Use of medications that are known to affect the study outcome measures Do not agree to use contraception throughout the study period in male and female participants of reproductive and childbearing age Persons who are not able to grant voluntary informed consent Unable or unwilling to follow the study protocol Have any other condition not listed in this section (e.g. hypersensitivity or intolerance) that is a contraindication of GLP-1R agonists