Morbid ObesityPhase 4NCT07859176
Tapered Versus Abrupt Discontinuation of Semaglutide After Treatment of Recurrent Weight Gain or Suboptimal Response Following Metabolic and Bariatric Surgery
A Phase 4 study testing Semaglutide weekly injection in people with Morbid Obesity, run by General Committee of Teaching Hospitals and Institutes, Egypt at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Morbid Obesity
- What is being tested?
- Semaglutide weekly injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteEgypt
- Study dates
- Oct 2026to Apr 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Egypt1 site
The surgical department of Medical Research Institute Hospital, Alexandria University
Alexandria, 21531
Mohamed Hany Ashour, Professor, MD, +201002600970, mohamed.ashour@alexu.edu.eg
Mohamed Hany Ashour, Professor, MD, mohamed.ashour@alexu.edu.eg
About this study
Official title: Tapered Versus Abrupt Discontinuation of Semaglutide After Treatment of Recurrent Weight Gain or Suboptimal Response Following Metabolic and Bariatric Surgery: a Randomized, Double-blind Trial
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.
Read more
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.
Read the 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.
- Conditions
- Morbid Obesity
- Being tested
- Semaglutide weekly injection, Placebo
- Keywords
- TAPER, Tapered versus abrupt discontinuation of semaglutide, semaglutide, recurrent weight gain, suboptimal response, metabolic and bariatric surgery, bariatric surgery
- Medical subject headings
- Obesity, Morbid, Weight Gain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semaglutide weekly injectionDrug
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.
PlaceboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Taper | Active comparator | 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. Receives: Drug: Semaglutide weekly injection |
| Abrupt | Placebo comparator | matched placebo pens on the identical schedule from week 0; injections stop at week 16. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage change in body weight
Measured in kilograms from randomization to month 12, measured on the same calibrated scale, morning, light clothing.
Measured: Baseline till 18 months
Secondary outcomes (9)
Weight change
measured in kilograms
Measured: 6, 18 months
Proportion weight
regaining more than 25% and more than 50% of the weight lost during treatment.
Measured: baseline till 18 months
Recurrent weight gain
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).
Measured: Baseline till 18 months
Time to pharmacotherapy restart
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.
Measured: Baseline till 18 months
Hand-grip strength
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.
Measured: 0, 6, 12 months
waist circumference
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.
Measured: 0, 6, 12 months
change in HbA1c
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
Measured: 0, 6, 12 months
total cholesterol, LDL, HDL, and triglycerides
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.)
Measured: 0, 6, 12 months
De novo restrictive eating behavior
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.
Measured: 0, 6, 12, 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2026
- Study startOct 2026 (estimated)
- Primary completionApr 2028 (estimated)
- Study completionApr 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Morbid ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- General Committee of Teaching Hospitals and Institutes, Egypt
- Sponsor type
- Other government
- Responsible party
- Principal investigator, Mohamed Hany Ashour, General Committee of Teaching Hospitals and Institutes, Egypt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07859176
- Sponsor's protocol ID
- TAPER Trial
- Status last verified
- Sep 2026
- First submitted
- 29 Sep 2026
- Last updated
- 5 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tapered Versus Abrupt Discontinuation of Semaglutide After Treatment of Recurrent Weight Gain or Suboptimal Response Following Metabolic and Bariatric Surgery: a Randomized, Double-blind Trial
- ClinicalTrials.gov ID
- NCT07859176
- Acronym / sponsor ID
- TAPER Trial
- Conditions
- Morbid Obesity
- Keywords
- TAPER, Tapered versus abrupt discontinuation of semaglutide, semaglutide, recurrent weight gain, suboptimal response, metabolic and bariatric surgery, bariatric surgery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- General Committee of Teaching Hospitals and Institutes, EgyptOther government
- Study start
- Oct 2026 (estimated)
- Primary completion
- Apr 2028 (estimated)
- Study completion
- Apr 2028 (estimated)
- First posted
- 5 Oct 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Taper | Active comparator | Drug: Semaglutide weekly injectionactive 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. |
| Abrupt | Placebo comparator | Drug: Placebomatched placebo pens on the identical schedule from week 0; injections stop at week 16. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Semaglutide weekly injectionActive 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. | Drug | Taper |
| PlaceboMatched 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. | Drug | Abrupt |
Primary outcome
Percentage change in body weight
Time frame: Baseline till 18 months
Measured in kilograms from randomization to month 12, measured on the same calibrated scale, morning, light clothing.
9 secondary outcomes
Weight change
Time frame: 6, 18 months
Proportion weight
Time frame: baseline till 18 months
Recurrent weight gain
Time frame: Baseline till 18 months
Time to pharmacotherapy restart
Time frame: Baseline till 18 months
Hand-grip strength
Time frame: 0, 6, 12 months
waist circumference
Time frame: 0, 6, 12 months
change in HbA1c
Time frame: 0, 6, 12 months
total cholesterol, LDL, HDL, and triglycerides
Time frame: 0, 6, 12 months
De novo restrictive eating behavior
Time frame: 0, 6, 12, 18 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2026.
- Individual participant dataSharing planned: Yes
Related trials for Morbid Obesity
Not yet recruitingObservational study
Pilot Study on the Effectiveness and Safety of OPTILENE® SILVER MESH ELASTIC in Prevention of Surgical Site Infection (SSI) and Incisional Hernia (IH)
Abdominal Aortic Aneurysm, Morbid Obesity
Not yet recruitingObservational study
Evaluating Metabolic Health in Individuals With Extreme Obesity
BMI>40
Enrolling by invitationObservational study
Bariatric Surgery Registry
Obesity, Morbid
Not yet recruitingObservational study
Serum Estradiol and Endometrial Thickness After Bariatric Surgery in Postmenopausal Women With Obesity
Obesity, Morbid, Postmenopause
Active, not recruiting
Mindfulness Based Eating Awareness Training for Bariatric Surgery Patients
Obesity, Morbid, Eating Disorder Symptom
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Semaglutide weekly injection in people with Morbid Obesity, run by General Committee of Teaching Hospitals and Institutes, Egypt at 1 site in Egypt.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 5 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Egypt. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mohamed Hany Ashour, Professor, MD (+201002600970, mohamed.ashour@alexu.edu.eg), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage change in body weight (time frame: Baseline till 18 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2026.