Morbid Obesity
Conditions
Keywords
Semaglutide, primary metabolic and bariatric surgery, bariatric surgery, BMI 60 kg/m² or higher
Brief summary
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.
Detailed description
Operative difficulty can be measured properly. Our group's surgical video assessment methodology makes it the primary endpoint: every operation is recorded in full, anonymized, and rated independently by three blinded expert surgeons using a predefined five-domain instrument (liver size and handling, quality of exposure, tissue fragility and adhesions, bleeding tendency, overall difficulty). The surgeon cannot be blinded to the patient's habitus on the table; the raters watching the video are blinded to allocation. This gives a blinded, objective primary endpoint in an unblindable operation. Perioperative drug handling follows the 2025 multisociety guidance: last injection at least 7 days before surgery, 24 hours of clear fluids, and full-stomach precautions at induction (PMID 39480373). This is written into the protocol, not left to the anesthesia team on the day. Unlike our SANDWICH population, these patients will not lose their surgical indication. From BMI 60, even an excellent 16-week response leaves the patient far above every operative threshold. The deferral rule is retained for completeness, and every patient is analyzed in the assigned arm, but exit from surgery is not a realistic outcome here. This trial is about making an unavoidable operation better. Both answers change practice. If the drug makes surgery measurably easier and safer, a 16-week semaglutide bridge becomes the standard pathway for the highest-BMI patients, in line with the direction of the 2024 IFSO position on combining pharmacotherapy with surgery (PMID 39400870). If it does not, the trial stops an expensive drift in practice before it hardens into habit. Question: In adults with BMI 60 kg/m² or higher undergoing primary laparoscopic SG or RYGB, does 16 weeks of preoperative semaglutide make the operation objectively easier and safer than the standard preoperative program alone? Primary hypothesis. Preoperative semaglutide lowers the blinded video-rated operative difficulty score by at least 0.65 standard deviations. Secondary hypothesis. Preoperative semaglutide shortens operative time, reduces intraoperative adverse events, and does not increase postoperative complications.
Interventions
Weeks 0 to 16: semaglutide 0.25, 0.5, 1.0, 1.7, then 2.4 mg weekly in 4-weekly steps, or matched placebo. Slower escalation allowed for tolerance; minimum acceptable plateau 1.7 mg. Last injection at least 7 days before surgery. Clear fluids for 24 hours before induction. Anesthesia manages every trial patient with full-stomach precautions. Surgery in weeks 17 to 18: laparoscopic SG or RYGB by the standardized unit technique, chosen and declared before randomization. Every operation recorded in full.
DRUGPlacebo
Matched placebo pens on the identical schedule
Sponsors
General Committee of Teaching Hospitals and Institutes, Egypt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* BMI 60 kg/m² or higher at first surgical assessment * Accepted by the multidisciplinary team for primary laparoscopic SG or RYGB * Able to self-inject and consent
Exclusion criteria
* Any previous bariatric or major upper abdominal surgery * GLP-1-based therapy within the previous 6 months * Type 1 diabetes * Pregnancy or conception planned within the study (obesity pharmacotherapy is stopped at least 2 months before any planned conception, per current labeling and the 2026 Standards) * Personal or family history of medullary thyroid carcinoma or MEN2 * History of pancreatitis * Active severe gastrointestinal disease * Any condition making 16 weeks of delay unsafe in the judgment of the surgical team
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean operative difficulty score | At the time or during surgery | Each anonymized video is rated independently by three blinded expert bariatric surgeons on five domains (liver size and handling; exposure; tissue fragility and adhesions; bleeding tendency; overall difficulty), each 1 to 5, total 5 to 25. The mean of the three raters is the patient's score. Raters are trained on a calibration set of 10 non-trial videos before unblinded rating begins; inter-rater reliability (ICC) is reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Preoperative percentage of total weight loss (%TWL) | from week 0 to surgery | Total weight loss measured in Kilograms |
| Operative time, skin to skin | At the time or during surgery | From the start till the end of the surgery measured in minutes |
| Estimated blood loss | At the time of surgery | Bleeding intraoperative measured in milliliters |
| Intraoperative adverse events | At the time or during surgery | Adverse intraoperative events (AIEs) occur in approximately 3% to 7% of bariatric surgeries and increase the relative risk of overall postoperative complications by about 90%. * Organ Injuries: Unintentional lacerations or punctures to the liver, spleen, stomach, intestines, or major blood vessels during trocar placement or dissection. * Intraoperative Bleeding: Significant hemorrhage from staple lines, mesentery, or the abdominal wall requiring intervention or transfusion. * Anastomosis and Staple Line Issues: Leaks, bleeding, or technical difficulties during the creation of pouches or connections (such as in a Roux-en-Y Gastric Bypass), identified via intraoperative leak tests. * Equipment Malfunction: Failures involving laparoscopic staplers, cameras, insufflation systems, or energy devices. * Anesthesia-Related Events: Severe hemodynamic instability, difficult airway management, or allergic reactions linked to medications. |
| Conversion to open | At the time or during surgery | Number of cases converted from laparoscopic to open surgery. |
| Number of stapler loads | At the time or during surgery | Number of stapler loads in each case. |
| 30-day complications | From surgery until 12 months postoperative | The Clavien-Dindo Classification grades 30-day postoperative complications based on the level of medical or surgical therapy needed to treat them. Grade I: Any deviation from the normal postoperative course without the need for pharmacological treatment or surgical, endoscopic, and radiological interventions. Grade II: Requiring pharmacological treatment with drugs other than those allowed for Grade I, including blood transfusions and total parenteral nutrition. Grade III: Requiring surgical, endoscopic, or radiological intervention. Grade IIIa: Intervention not under general anesthesia. Grade IIIb: Intervention under general anesthesia. Grade IV: Life-threatening complication (including central nervous system complications) requiring intermediate care or intensive care unit (ICU) management. Grade V: Death of a patient. |
| Liver span | At week 0 and week 16 | By standardized ultrasound A normal adult liver span measured by ultrasound along the midclavicular line is typically less than 15 to 16 cm in the craniocaudal (vertical) dimension. Right Lobe (Craniocaudal): Usually 13 to 15 cm; values above 15-16 cm often suggest hepatomegaly (enlarged liver). Left Lobe (Width/Thickness): Usually less than 7 cm. |
| Hand-grip strength | At week 0, week 16, and month 12 | A hand grip strength test measures the maximum force of your hand and forearm muscles using a portable device called a handgrip dynamometer. Position yourself: Sit up straight with your feet flat on the floor. Place your arm by your side with your elbow bent at a 90-degree angle and your wrist in a neutral position. Hold the device: Adjust the handle so it fits comfortably in your hand. Squeeze hard: Squeeze the handles as hard as you can for about 3 to 5 seconds without moving your arm or resting the device against your body. Repeat trials: Take three measurements for each hand, resting for 15 to 30 seconds between attempts. Use either the highest score or the average of the trials. A normal hand grip strength score typically ranges from 40 to 56 kg (88 to 123 lbs) for adult men and 25 to 36 kg (55 to 79 lbs) for adult women aged 20-29. |
| Waist circumference | At week 0, week 16, and month 12 | Waist circumference is a direct measurement of belly fat that helps assess your risk for chronic health issues like heart disease and type 2 diabetes. Health risk increases when waist size goes past certain thresholds: * Men: High risk starts above 102 cm (40 inches) according to standard guidelines, though some organizations flag risks starting at 94 cm (37 inches). * Women: High risk starts above 88 cm (35 inches), with tighter thresholds starting at 80 cm (31.5 inches) in some regional guidelines. |
| Safety of the drug phase | From enrollment until 16 weeks | Of semaglutide including gastrointestinal adverse events and any aspiration event at induction. |
Countries
Egypt
Contacts
CONTACTMohamed Hany Ashour, Professor, MD
Outcome results
None listed