Clinical trials

Metabolic and bariatric surgery (MBS) is the most effective durable treatment for severe obesity, yet a clinically meaningful proportion of patients experience recurrent weight gain after an initially successful operation. Until recently, research and care in this area were limited by the absence of standardized definitions: reported prevalence of weight recurrence ranged from under 10% to over 90% depending on the metric and threshold applied, and treatment decisions varied by provider. In 2026, an international two-round modified Delphi study of 66 experts across surgery, obesity medicine, gastroenterology, endocrinology, dietetics, and psychology (Wills et al.) established consensus definitions. The consensus specifies: (i) percentage total weight loss (%TWL) as the preferred measurement approach (94.6% agreement); (ii) surgical non-response as \<10% TWL at 12 months (73.0%); (iii) recurrent weight gain as regain of more than 25% of lost weight from nadir (70.3%); and (iv) a change of up to 10% in percentage excess weight loss from nadir as a normal physiologic fluctuation not requiring intervention (83.8%). The consensus also endorsed 'suboptimal' as the preferred terminology for poor surgical response and reached unanimous agreement that anti-obesity medications may appropriately be prescribed by specialists in this population. These definitions supersede the heterogeneous thresholds used previously, including the \>30% regain threshold of the 2024 IFSO Delphi, and are adopted throughout this protocol. Both IFSO and ASMBS now formally support pharmacotherapy as a therapeutic option for weight recurrence after MBS. The 2024 IFSO international consensus on obesity management medications in the context of MBS reinforces this pathway: at 92% agreement, medications should generally be considered before revisional surgery for recurrent weight gain; at 100%, medication efficacy appears broadly preserved after MBS; and at 97%, no clear increase in adverse effects after MBS has been demonstrated. RESURGE supplies the randomized evidence behind the first of these statements.

Recurrent weight gain affects 15% to 40% of patients after metabolic and bariatric surgery (MBS). SG is the most performed operation worldwide, and long-term regain after SG is well documented. A 2026 international Delphi consensus has now standardized the definition. This trial uses that definition. So does our companion trial, RESURGE. We have two real treatments. Both work. Neither is enough. Conversion of SG to RYGB gives around 20% additional total weight loss at 12 months across all indications, and less when the indication is poor weight response rather than reflux. Drug therapy also works after MBS. Liraglutide beat placebo by about 8 percentage points in the BARI-OPTIMISE randomized trial. Semaglutide gives around 11% total weight loss and tirzepatide around 14% in pooled retrospective data, including specifically after SG. Most patients do not return to their nadir weight with either option alone. The field is already comparing the two strategies, but only retrospectively. Two 2025 multicenter cohorts compared conversion against GLP-1 therapy after SG. These studies cannot control diet, exercise, supplementation, co-medication, or adherence. They cannot settle the question. The societies agree on the pathway but admit the evidence is weak. The 2024 IFSO position statement and the 2026 ASMBS statement say the same thing: work up the anatomy first; operate when there is a structural problem; consider medical therapy when there is not; and consider combining drug therapy with revision. The 2024 IFSO international consensus goes further: with 92% agreement, it states that medications should generally be considered before revisional surgery for recurrent weight gain. Every one of those recommendations rests on consensus and retrospective data. None rests on a randomized trial. This protocol is that trial.

Patients with BMI 60 kg/m² or higher are the hardest operations in bariatric surgery. Thick abdominal wall, massive hepatomegaly, reduced working space, fragile fatty tissue, higher conversion and complication rates. Every bariatric surgeon knows this group. Almost no trial recruits it. The standard answer is a short liver-reduction diet before surgery. It helps, but the effect is modest, hard to tolerate, and short-lived. GLP-1-based drugs now produce far larger and better-tolerated weight loss and are already being given before surgery in routine practice, without trial evidence. Retrospective series show more preoperative weight loss and no obvious harm, and no more than that (Obesity Research \& Clinical Practice 2026). A 2023 review of drugs on the surgical waiting list found that GLP-1 receptor agonists had never been evaluated for the preoperative indication at all. Two registered trials are now adjacent to this question, and we cite both. The PreMO pilot randomizes 50 patients to open-label preoperative tirzepatide versus standard care, with tissue inflammation as the scientific focus (PMID 41643256; NCT06721507). A three-arm trial before one-anastomosis gastric bypass compares tirzepatide, ketogenic diet, and standard care, with weight loss at one year as primary (NCT07622992). Neither is blinded. Neither recruits BMI 60 and above. Neither measures whether the drug actually makes the operation easier and safer. The 2024 IFSO international consensus reached 100% agreement that evidence is insufficient to recommend routine preoperative medication, that use must be individualized, and that more research on benefits, risks, and outcomes is required; it also agreed, at 97%, that adequate protein and resistance exercise must accompany any preoperative drug treatment (PMID 39612579). This trial is the research that consensus calls for, and its preoperative program is built to the 97% requirement.

Every course of obesity pharmacotherapy ends. Cost, supply, pregnancy plans, side effects, or the patient's own wish. In Egypt, cost alone makes discontinuation the rule, not the exception. Yet the entire evidence base describes what happens when the drug stops, and none of it tests how to stop. Abrupt withdrawal fails predictably. One year after stopping semaglutide, STEP 1 extension participants had regained two thirds of their lost weight. SURMOUNT-4 showed the same pattern after tirzepatide withdrawal, and meta-analysis confirms it across agents. After MBS specifically, stopping GLP-1 therapy is likewise followed by regain. The guidelines say: do not stop at all. The 2026 ADA and Obesity Association Standards strongly recommend continuing medication through maintenance, and the 2024 IFSO consensus agrees that when medication is needed to hold the benefit after MBS, ongoing treatment is probably necessary, while stating, at 94% agreement, that intermittent therapy and dose-reduction strategies require research. Our patients cannot follow the first recommendation. Cost decides for them. This trial is the research the second sentence asks for: the evidence for the moment when continuing is not an option. Clinicians already taper, on no evidence. A 2025 expert commentary describes 8-to-12-week dose reductions in routine practice and states plainly that the approach is anecdotal and untested (Obesity and Endocrinology 2025). Practice has run ahead of the trial. The general-population trial now exists, and we cite it rather than duplicate it. The REST trial has registered exactly this comparison, gradual 16-week dose reduction versus abrupt cessation, in non-surgical patients with obesity. No such trial exists after MBS.

Roughly one patient in five never reaches the expected weight loss after MBS, and long-term regain after SG is well documented. These patients are identifiable at the 12-month visit. Today they are watched, coached, and treated only when failure is established. Whether the drug works in this group is no longer the question. BARI-STEP, published this year, randomized 70 patients with less than 20% weight loss after gastric bypass (including one-anastomosis) or sleeve gastrectomy, a mean of seven years after surgery, to semaglutide 2.4 mg or placebo: 18.0% loss versus 0.4% gain at 68 weeks, an adjusted difference of 19.1 percentage points. Its population was mixed, 55.7% with recurrent weight gain and 44.3% with suboptimal initial response, and its exploratory comparison found no difference in drug response between the two presentations. BARI-OPTIMISE showed the same direction with liraglutide, as did a randomized trial after gastric banding. Efficacy is settled. Timing is not. BARI-STEP recruited patients a mean of seven years past surgery, after failure had hardened. No trial has tested treating at first recognition, the 12-month visit, against the current standard of structured waiting. The field's own reviews name timing and duration as the open questions. The 2024 IFSO international consensus reached 100% agreement that medication after MBS should generally be withheld until the weight plateau, and 100% agreement that adding it for a suboptimal response can then improve outcomes. That is exactly our immediate arm: treat at the plateau, at first recognition. The triggered arm is what clinics actually do: wait for established failure. Both positions rest on expert agreement, not on a trial. This is the randomized test of the consensus pathway. A registered open-label pilot starts tirzepatide at 12 or 18 months but is small, unblinded, and not a strategy comparison. The 2026 consensus draws the line for us, and this protocol respects it. The Delphi panel defined surgical nonresponse as less than 10% TWL at 12 months, defined recurrent weight gain as regain of more than 25% of lost weight from nadir, and treated a 10% swing in %EWL from nadir as normal physiologic fluctuation. It gave no 12-month label at all to the patient with 10 to 19.9% TWL, and the IFSO Delphi consensus expects the weight nadir up to 2 years after surgery (Obes Surg 2023). So a patient at 14% TWL at one year may still be on the way down, and calling that failure would be wrong. The protocol therefore splits eligibility into two tiers. Below 10% TWL at 12 months: consensus-defined nonresponse, randomized at once, waiting adds nothing. 10 to below 20% TWL: randomized only after a documented plateau, defined in Section 4, with a hard cap at month 18 so waiting cannot drift into neglect. Randomization is stratified by tier, and results are reported by tier.

Obesity remains a major global health challenge, with rising prevalence and significant metabolic, cardiovascular, and gastrointestinal comorbidities. Laparoscopic sleeve gastrectomy (LSG) has emerged as the most widely performed bariatric procedure due to its technical simplicity and satisfactory short- to mid-term results. However, a proportion of patients experience suboptimal weight loss, recurrent weight gain, or both. In this study, patients with recurrent weight gain of maximum weight loss or suboptimal weight loss or both following sleeve gastrectomy were included. Suboptimal weight loss is defined as total weight loss (TWL) of less than 20% of the preoperative weight and/or excess weight loss (EWL) of less than 50%, measured at least 12-18 months after the primary sleeve gastrectomy. Recurrent weight gain after sleeve gastrectomy is defined as an increase of ≥20% of the maximum weight loss (from nadir weight) or an increase in BMI of \>5, measured at least 24 months after the primary procedure.

Laparoscopic sleeve gastrectomy (LSG) has become an increasingly popular bariatric procedure since its first performance by Hess and Hess in 1988 as a component of the biliopancreatic diversion-duodenal switch (BPD-DS) procedure, which was modified from Scopinaro's biliopancreatic diversion (BPD) and DeMeester's technique. In the early part of the twenty-first century, it was popularized as a first-step intervention before BPD or gastric bypass in the super obese and high-risk group of patients by Regan et al. Due to the unexpected good results in terms of weight loss and resolution of comorbidities, coupled with the simplicity of performing the procedure requiring intervention on only the stomach, sleeve gastrectomy gained status as a stand-alone bariatric procedure as demonstrated by Baltasar et al. The basic principle of LSG is to create a narrow stomach along the lesser curvature, depending on the left gastric artery, using a calibration bougie as a template to perform a vertical partial gastrectomy, resecting the greater curvature and fundus of the stomach according to the International Sleeve Gastrectomy Expert Panel Consensus Statement by Rosenthal et al. The procedure has demonstrated excellent outcomes in terms of weight loss and comorbidity resolution, making it one of the most commonly performed bariatric procedures worldwide according to the IFSO Worldwide Survey by Angrisani et al. Bougie Size Considerations and Rationale The selection of an appropriate bougie size during laparoscopic sleeve gastrectomy represents a critical technical decision that significantly influences both immediate surgical outcomes and long-term patient results. Calibration bougies serve as internal templates to standardize the gastric sleeve diameter and ensure consistent sleeve geometry across different surgeons and institutions, as described by Parikh et al. The diameter of the bougie directly determines the final gastric volume and the degree of restriction achieved, which in turn affects weight loss efficacy, food tolerance, and complication rates. Bougie sizes in current clinical practice typically range from 32-French (Fr) to 50-Fr, with most centers utilizing sizes between 34-Fr and 42-Fr according to the survey by Gagner et al. Small bougie sizes (32-36-Fr) create a more restrictive sleeve with potentially enhanced weight loss but may be associated with increased risks of stenosis, food intolerance, and gastroesophageal reflux disease as reported by Sakran et al. Medium bougie sizes (38-42-Fr) represent a compromise between restriction and safety, offering adequate weight loss while maintaining acceptable complication rates as demonstrated by Weiner et al. Large bougie sizes (44-50-Fr) provide greater sleeve capacity with improved food tolerance and potentially reduced leak rates, though concerns exist regarding long-term weight loss maintenance according to Abdallah et al. The rationale for comparing different bougie sizes stems from the ongoing debate regarding the optimal balance between surgical efficacy and safety. Recent meta-analyses have suggested that larger bougie sizes may be associated with reduced gastric leak rates without significantly compromising weight loss outcomes. However, the majority of existing evidence comes from retrospective observational studies with inherent limitations including selection bias, confounding variables, and lack of standardized outcome measures as noted by Shi et al. The current study aims to provide definitive prospective evidence comparing small (36-Fr) versus X large (larger than 40-Fr) bougie sizes in a randomized controlled trial design. Furthermore, the impact of bougie size on comorbidity resolution remains inadequately studied. Bariatric surgery has demonstrated remarkable efficacy in resolving obesity-related comorbidities, with diabetes remission rates ranging from 53% to 63% as reported by Schauer et al. and hypertension resolution rates varying from 8% to 50% depending on the specific criteria used according to Sjöström et al. The relationship between sleeve geometry, as determined by bougie size, and comorbidity resolution mechanisms requires further investigation to optimize patient outcomes and surgical technique selection.

Assess what revisional surgery is superior and provides the best weight loss after primary LSG. What is the occurrence of complications and the nutritional laboratory status? And if the resolution and /or improvement of associated medical problems after the weight loss will occur.

SUMMARY Rationale: Prophylactic antibiotics in laparoscopic surgeries, including Metabolic Bariatric Surgery (MBS), are routinely provided to reduce postoperative infections, especially at wound incision sites. However, since incisional wound infections in laparoscopic MBS are rare and morbidity is very low, the benefit of antibiotic prophylaxis is questionable. Objective: Evaluate the non-inferiority of omitting antibiotic prophylaxis in MBS. Compare postoperative outcomes between Group A (no antibiotics) and Group B (standard antibiotic care) to determine if omission increases complications, particularly wound infections. Study Design: Randomized controlled trial (RCT), double-blind. Study Population: Patients with obesity eligible for MBS. Intervention: * Group A (No Antibiotic Prophylaxis): Undergo MBS without antibiotics to test safety regarding postoperative complications, focusing on surgical site infections (SSIs). * Group B (Standard Antibiotic Prophylaxis): Receive standard one-time antibiotics before incision. Main Study Parameters/Endpoints: Compare the incidence of incisional and organ/space SSIs within six weeks post-surgery between Group A and Group B to determine if omitting antibiotics affects infection rates.

Evaluating the differences between D2 and D3 lymphadenectomy in laparoscopic right hemicolectomy in patients with right cancer colon post-operative outcome, intra-operative blood transfusion, post-operative ICU admission, anastomotic leakage, lymph node harvesting in the final specimen, and six months follow up and overall survival time after 5-years