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

Obesity remains a major global health challenge. Metabolic and bariatric surgery (MBS) is the most effective treatment for severe obesity, but outcomes vary significantly among patients. This study investigates whether preoperative optimization with pharmacological treatment (tirzepatide) or dietary intervention (ketogenic diet) can improve long-term weight loss compared to proceeding directly to surgery without specific preoperative preparation. Tirzepatide is a dual GIP/GLP-1 receptor agonist that has shown remarkable efficacy in weight reduction trials. The ketogenic diet is a very-low-calorie approach that induces rapid weight loss while preserving lean body mass. However, no randomized trial has directly compared these strategies for preoperative optimization in MBS candidates. This multicenter randomized controlled trial will enroll 96 patients with severe obesity (BMI 45-55 kg/m²) scheduled for One Anastomosis Gastric Bypass (OAGB). Participants will be randomized 1:1:1 to three arms: (A) tirzepatide treatment for 60 days with dose escalation (2.5 mg → 5 mg → 7.5 mg weekly subcutaneous injections); (B) supervised ketogenic diet for 4 weeks (700 kcal/day with less than 50g carbohydrates); or (C) standard preoperative care without specific intervention. All participants will undergo standardized OAGB surgery performed by experienced surgeons. The primary endpoint is percentage of total weight loss at 12 months post-surgery. Secondary endpoints include perioperative outcomes (operative time, complications, hospital stay), resolution of obesity-related comorbidities (diabetes, hypertension, dyslipidemia, sleep apnea), nutritional status. Randomization will be stratified by baseline BMI category, presence of type 2 diabetes, and participating center to ensure balance across important prognostic factors. Follow-up visits will occur at 30 days, 3 months, 6 months, and 12 months post-surgery with comprehensive clinical and laboratory assessments. This study will provide crucial evidence to guide clinical decision-making regarding optimal preoperative management strategies for patients undergoing bariatric surgery, addressing the balance between potential benefits of preoperative weight loss and surgical safety.