Preoperative Optimization With Tirzepatide, Ketogenic Diet, or Standard Care Before One Anastomosis Gastric Bypass Surgery

Inclusion Criteria: * Age 18 to 65 years at enrollment * Body Mass Index (BMI) between 40 and 55 kg/m² at screening visit * Appropriate candidates for bariatric surgery according to current international guidelines (IFSO 2022) with documented failure of conservative weight loss attempts * Presence of at least one obesity-related comorbidity: Type 2 Diabetes Mellitus (HbA1c at least 6.5%, fasting plasma glucose at least 126 mg/dL, 2-hour OGTT glucose at least 200 mg/dL, or use of antidiabetic medications); Hypertension (systolic BP at least 140 mmHg or diastolic BP at least 90 mmHg, or use of antihypertensive medications); Dyslipidemia (total cholesterol at least 200 mg/dL, LDL-C at least 130 mg/dL, HDL-C less than 40 mg/dL for men or less than 50 mg/dL for women, triglycerides at least 150 mg/dL, or use of lipid-lowering medications); Obstructive Sleep Apnea Syndrome (AHI at least 15 events/hour or AHI 5-14 with symptoms requiring treatment) * Ability to understand study procedures and provide written informed consent * Demonstrated ability and willingness to adhere to study protocol requirements including preoperative interventions and postoperative follow-up visits * No use of GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists within 12 months prior to enrollment Exclusion Criteria: * History of any prior bariatric procedure or major upper gastrointestinal surgery that could confound outcomes or increase surgical risk * Severe uncontrolled psychiatric disorders including active psychosis, severe depression with suicidal ideation, active substance abuse, or eating disorders (other than binge eating disorder) that could impair protocol adherence or informed consent capacity * Current pregnancy, lactation, or planning pregnancy within 18 months of enrollment (women of childbearing potential must use effective contraception throughout study period) * Contraindications to tirzepatide for patients potentially randomized to Arm A: personal or family history of medullary thyroid carcinoma; Multiple Endocrine Neoplasia syndrome type 2 (MEN 2); history of pancreatitis; severe gastrointestinal disease (inflammatory bowel disease, gastroparesis); known hypersensitivity to tirzepatide or excipients * Contraindications to ketogenic diet for patients potentially randomized to Arm B: chronic kidney disease (eGFR less than 30 mL/min/1.73m²); severe hepatic insufficiency (Child-Pugh C); active gallbladder disease; history of kidney stones; porphyria; carnitine deficiency or other metabolic disorders * Current or recent malignancy (within 5 years) at any stage * Severe cardiopulmonary disease including recent myocardial infarction (less than 6 months), unstable angina, heart failure (NYHA class III-IV), severe pulmonary hypertension, or other conditions representing absolute contraindications to general anesthesia * Systemic infection requiring treatment at time of enrollment * Inability or unwillingness to attend required follow-up visits, language barriers preventing adequate communication, or any condition that would compromise protocol compliance