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Tapered Versus Abrupt Discontinuation of Semaglutide After Treatment of Recurrent Weight Gain or Suboptimal Response Following Metabolic and Bariatric Surgery

29 de septiembre de 2026 actualizado por: Mohamed Hany Ashour, General Committee of Teaching Hospitals and Institutes, Egypt

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.

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.

Descripción general del estudio

Estado

Aún no reclutando

Condiciones

Descripción detallada

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.

Tipo de estudio

Intervencionista

Inscripción (Estimado)

100

Fase

  • Fase 4

Contactos y Ubicaciones

Esta sección proporciona los datos de contacto de quienes realizan el estudio e información sobre dónde se lleva a cabo este estudio.

Estudio Contacto

Ubicaciones de estudio

      • Alexandria, Egipto, 21531
        • The surgical department of Medical Research Institute Hospital, Alexandria University
        • Contacto:
        • Contacto:

Criterios de participación

Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.

Criterio de elegibilidad

Edades elegibles para estudiar

18 años a 65 años (Adulto, Adulto Mayor)

Acepta Voluntarios Saludables

No

Géneros elegibles para el estudio

Todos

Descripción

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

Plan de estudios

Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.

¿Cómo está diseñado el estudio?

Detalles de diseño

  • Propósito principal: Tratamiento
  • Asignación: Aleatorizado
  • Modelo Intervencionista: Asignación paralela
  • Enmascaramiento: Cuadruplicar

Armas e Intervenciones

Grupo de participantes/brazo
Intervención / Tratamiento
Comparador activo: Taper

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.

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.

Comparador de placebos: Abrupt

matched placebo pens on the identical schedule from week 0; injections stop at week 16.

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.

¿Qué mide el estudio?

Medidas de resultado primarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Percentage change in body weight
Periodo de tiempo: Baseline till 18 months

Measured in kilograms from randomization to month 12, measured on the same calibrated scale, morning, light clothing.

Baseline till 18 months

Medidas de resultado secundarias

Medida de resultado
Medida Descripción
Periodo de tiempo
Hand-grip strength
Periodo de tiempo: 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.

0, 6, 12 months
Weight change
Periodo de tiempo: 6, 18 months

measured in kilograms

6, 18 months
Proportion weight
Periodo de tiempo: baseline till 18 months

regaining more than 25% and more than 50% of the weight lost during treatment.

baseline till 18 months
Recurrent weight gain
Periodo de tiempo: 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).
Baseline till 18 months
Time to pharmacotherapy restart
Periodo de tiempo: 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.

Baseline till 18 months
waist circumference
Periodo de tiempo: 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.

0, 6, 12 months
change in HbA1c
Periodo de tiempo: 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

0, 6, 12 months
total cholesterol, LDL, HDL, and triglycerides
Periodo de tiempo: 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.)

0, 6, 12 months
De novo restrictive eating behavior
Periodo de tiempo: 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.

0, 6, 12, 18 months

Colaboradores e Investigadores

Aquí es donde encontrará personas y organizaciones involucradas en este estudio.

Fechas de registro del estudio

Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados ​​por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.

Fechas importantes del estudio

Inicio del estudio (Estimado)

1 de octubre de 2026

Finalización primaria (Estimado)

1 de abril de 2028

Finalización del estudio (Estimado)

1 de abril de 2028

Fechas de registro del estudio

Enviado por primera vez

29 de septiembre de 2026

Primero enviado que cumplió con los criterios de control de calidad

29 de septiembre de 2026

Publicado por primera vez (Actual)

5 de octubre de 2026

Actualizaciones de registros de estudio

Última actualización publicada (Actual)

5 de octubre de 2026

Última actualización enviada que cumplió con los criterios de control de calidad

29 de septiembre de 2026

Última verificación

1 de septiembre de 2026

Más información

Términos relacionados con este estudio

Plan de datos de participantes individuales (IPD)

¿Planea compartir datos de participantes individuales (IPD)?

SÍ

Tipo de información de apoyo para compartir IPD

  • PROTOCOLO DE ESTUDIO
  • SAVIA
  • CIF
  • CÓDIGO_ANALÍTICO
  • RSC

Información sobre medicamentos y dispositivos, documentos del estudio

Estudia un producto farmacéutico regulado por la FDA de EE. UU.

No

Estudia un producto de dispositivo regulado por la FDA de EE. UU.

No

Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .

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