Morbid Obesity
Conditions
Keywords
TAPER, Tapered versus abrupt discontinuation of semaglutide, semaglutide, recurrent weight gain, suboptimal response, metabolic and bariatric surgery, bariatric surgery
Brief summary
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.
Detailed description
The post-surgical patient is not the same patient. Foregut anatomy and endogenous incretin dynamics are altered, the operation provides a durable anatomical base that may protect against rebound, and the surgical program offers a defined rescue pathway if recurrence returns. Whether tapering matters in this physiology is a separate question with a separate answer, and it is the question our patients actually face at the end of RESURGE, SANDWICH, and TOP-UP. The design makes blinding nearly free. The abrupt arm injects matched placebo on the same 16-week schedule, so neither the patient nor the team knows who is weaning. This removes expectation effects on appetite and eating behavior, which are exactly the outcomes a discontinuation trial must protect. Either answer changes practice immediately. If tapering preserves weight, it becomes the standard exit ramp for every patient finishing GLP-1 therapy after MBS. If it does not, patients stop paying for 16 extra weeks of drug for nothing. For a health system like ours, both answers are worth having.
Interventions
Active pens at 1.7 mg for 4 weeks, then 1.0, 0.5, and 0.25 mg for 4 weeks each; injections stop at week 16. Maintenance program throughout: dietitian visits at months 0, 1, 2, 4, and then every 2 months; protein maintained at 60-80 g/day (1.0-1.5 g/kg ideal body weight, ERAS guidance); 150 minutes of weekly activity plus resistance training twice weekly; wrist accelerometer worn continuously. Restart rule: after month 6, open-label pharmacotherapy may be restarted only if the Delphi recurrence criteria are met; every restart is recorded and the patient stays in follow-up. The primary analysis is treatment-policy; a hypothetical estimand ignoring restart is a supporting analysis.
DRUGPlacebo
Matched placebo pens on the identical schedule from week 0; injections stop at week 16. Maintenance program throughout: dietitian visits at months 0, 1, 2, 4, and then every 2 months; protein maintained at 60-80 g/day (1.0-1.5 g/kg ideal body weight, ERAS guidance); 150 minutes of weekly activity plus resistance training twice weekly; wrist accelerometer worn continuously. Restart rule: after month 6, open-label pharmacotherapy may be restarted only if the Delphi recurrence criteria are met; every restart is recorded and the patient stays in follow-up. The primary analysis is treatment-policy; a hypothetical estimand ignoring restart is a supporting analysis.
Sponsors
General Committee of Teaching Hospitals and Institutes, Egypt
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Patients, clinicians, dietitians, and assessors blinded; pharmacy-controlled identical pens; unblinding only for safety. Pens are matched step by step: at each 4-week taper step both arms receive pens of identical appearance for that step, active descending doses in the taper arm and placebo in the abrupt arm, so the dose sequence itself cannot unblind.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Previous MBS of any type * On semaglutide 2.4 mg (or maximum tolerated dose of at least 1.7 mg) for at least 6 months * prescribed for recurrent weight gain or suboptimal response * Weight stable within 3% over the last 12 weeks * Patient and physician have decided to discontinue
Exclusion criteria
* Type 2 diabetes requiring continued GLP-1 therapy * Planned revisional surgery within the study period * 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, and such patients follow that pathway, not this protocol * Concurrent use of any other obesity medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage change in body weight | Baseline till 18 months | Measured in kilograms from randomization to month 12, measured on the same calibrated scale, morning, light clothing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weight change | 6, 18 months | measured in kilograms |
| Proportion weight | baseline till 18 months | regaining more than 25% and more than 50% of the weight lost during treatment. |
| Recurrent weight gain | Baseline till 18 months | Recurrent weight gain (RWG) is defined by the July 2026 international Delphi consensus as gaining more than 25% of the weight that was initially lost from the post-surgical nadir (the lowest weight point achieved after metabolic and bariatric surgery) Panel and Scope: A two-round modified Delphi study published in mid-2026 involved 66 international experts across five medical specialties to standardize definitions following metabolic and bariatric surgery (MBS) Preferred Terminology: The panel established "suboptimal" as the preferred overarching term (89.5% consensus) Optimal Measurement Metric: Percentage of Total Weight Loss (%TWL) was voted the optimal measurement approach (94.6% consensus) Related Thresholds: * Surgical nonresponse: Less than 10% TWL at 12 months (73.0% consensus). * Normal physiologic response: A 10% fluctuation in percentage of excess weight loss (%EWL) from the nadir (83.8% consensus). |
| Time to pharmacotherapy restart | Baseline till 18 months | Restart rule: after month 6, open-label pharmacotherapy may be restarted only if the Delphi recurrence criteria are met; every restart is recorded and the patient stays in follow-up. The primary analysis is treatment-policy; a hypothetical estimand ignoring restart is a supporting analysis. |
| Hand-grip strength | 0, 6, 12 months | 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 | 0, 6, 12 months | 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. |
| change in HbA1c | 0, 6, 12 months | An HbA1c level reflects your average blood sugar over the past two to three months, and any meaningful change typically takes at least 6 weeks to show because red blood cells live for about 3 months. Normal: Below 5.7% Prediabetes: 5.7% to 6.4% Diabetes: 6.5% or higher |
| total cholesterol, LDL, HDL, and triglycerides | 0, 6, 12 months | Normal adult values for a lipid panel are measured in milligrams per deciliter (mg/dL): • Total Cholesterol: Below 200 mg/dL is desirable. (Borderline high is 200-239 mg/dL, and high is 240 mg/dL and above.) • LDL ("Bad") Cholesterol: Below 100 mg/dL is optimal. (130-159 mg/dL is borderline high, and 160-189 mg/dL or higher is high.) • HDL ("Good") Cholesterol: 60 mg/dL and higher is protective. Levels below 40 mg/dL for men or below 50 mg/dL for women are considered low. • Triglycerides: Below 150 mg/dL is normal. (Borderline high is 150-199 mg/dL, and high is 200-499 mg/dL.) |
| De novo restrictive eating behavior | 0, 6, 12, 18 months | Is an adverse event of special interest, after the single suspected unexpected serious adverse reaction in BARI-STEP; investigators screen for it at every visit, with an urgent psychology referral pathway. |
Countries
Egypt
Contacts
CONTACTMohamed Hany Ashour, Professor, MD
Outcome results
None listed