Preoperative Optimization With Tirzepatide, Ketogenic Diet, or Standard Care Before One Anastomosis Gastric Bypass Surgery (OPTI-OAGB)

Efficacy of Preoperative Tirzepatide, Ketogenic Diet, and Standard Care on 1-Year Weight Loss After One Anastomosis Gastric Bypass (OAGB)

This study compares three preoperative strategies before one anastomosis gastric bypass(OAGB) for severe obesity. Participants will be assigned to receive either tirzepatide medication for 60 days, a ketogenic diet for 4 weeks, or standard care before surgery. The main goal is to determine which approach leads to the best weight loss one year after surgery. The study will also evaluate safety, surgical outcomes, and improvement of obesity-related health conditions such as diabetes, high blood pressure, and sleep apnea.

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity (BMI > 35) and Diabetes Mellitus; Obesity (BMI > 35) and High Blood Pressure; Obesity (BMI > 35) and Dyslipemia

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 96

Contacts and Locations

• Study Contact: Name: Mario Musella Prof, MD; Phone Number: 0039 0817462880; Email: mario.musella@unina.it

Study Locations

• Italy
  • Italy
    • Naples, Italy, Italy, 80131
      • University Federico II of Naples
      • Contact: Mario Musella Prof, MD; Phone Number: 0039 0817462880; Email: mario.musella@unina.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients between 18 to 65 years, with Body Mass Index (BMI) between 40 and 55 kg/m² at screening visit. The patients must be eligible for bariatric surgery according to current international guidelines (IFSO 2022) with documented failure of conservative weight loss attempts. Patients enrolled need to have at least one obesity-related comorbidity and the ability to understand study procedures and provide written consent.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Ketogenic Diet 4 Weeks; Participants undergo supervised very-low-calorie ketogenic diet (VLCKD) for 4 weeks immediately before OAGB surgery.
Standard Care Control; Participants undergo standard preoperative preparation without specific medical or dietary intervention. Includes standard multidisciplinary evaluation (surgeon, dietitian, psychologist, anesthesiologist), general nutritional counseling, encouragement to maintain current weight and avoid weight gain, no structured calorie restriction or specific dietary protocol, and no GLP-1 receptor agonist or weight loss pharmacotherapy
Tirzepatide 60 Days; Participants receive tirzepatide (Mounjaro®) subcutaneously once weekly for 60 days prior to OAGB surgery following dose escalation protocol: Weeks 1-4: 2.5 mg weekly; Weeks 5-8: 5 mg weekly; Week 9 (if tolerated): 7.5 mg weekly. Tirzepatide discontinued 7 days before surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Total Weight Loss at 1 Year Post-Surgery	The primary endpoint is the percentage of total weight loss (%TWL) measured at 12 months after bariatric surgery. %TWL is calculated as: [(Baseline Weight - Weight at 12 months) / Baseline Weight] × 100	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Excess Weight Loss at 1 Year	Percentage of excess weight loss (%EWL) calculated as: [(Baseline Weight - Weight at 12 months) / (Baseline Weight - Ideal Body Weight)] × 100, where Ideal Body Weight is calculated using the Devine formula	1 year
Absolute Weight Loss at 1 Year	Absolute weight loss measured in kilograms (kg), calculated as the difference between baseline weight (at randomization) and weight at 12 months post-surgery	1 year

Collaborators and Investigators

• Sponsor: Mario Musella MD

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: May 28, 2026
• First Submitted That Met QC Criteria: May 28, 2026
• First Posted (Actual): June 3, 2026

Study Record Updates

• Last Update Posted (Actual): June 3, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Bariatric Surgery; Ketogenic Diet; Tirzepatide; OAGB
• Additional Relevant MeSH Terms: Endocrine System Diseases; Vascular Diseases; Cardiovascular Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Hypertension; Diabetes Mellitus
• Other Study ID Numbers: OPTI-OAGB Trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Protocol and results
• IPD Sharing Time Frame: From 2029 for 1 year
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No