Actively Recruiting

Phase 3
Age: 18Years - 75Years
All Genders
ID07294950

Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: a Randomized Controlled Trial Comparing Gradual Dose Reduction With Immediate Treatment Cessation

Led by Mount Sinai Hospital, Canada · Updated on 2026-02-11

98

Participants Needed

1

Research Sites

34 weeks

Total Duration

On this page

Sponsors

M

Mount Sinai Hospital, Canada

Lead Sponsor

H

Heart and Stroke Foundation of Canada

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are studying the effects of gradually reducing semaglutide compared to stopping it all at once in adults living with obesity who have no pre-existing cardiovascular disease or type 2 diabetes. Semaglutide is a medication that helps with weight loss by affecting appetite control, but little is known about the best way to maintain weight after stopping this treatment. This trial aims to understand if tapering off semaglutide affects weight regain, heart risk factors, and hormones that regulate energy differently than stopping immediately. The study involves two groups: one group will reduce their semaglutide dose by 25% every four weeks until stopping completely at week 16, while the other group will stop semaglutide all at once at week 16. This open-label trial will compare changes in body weight, blood pressure, and hormone levels related to appetite and energy balance between these groups over 32 weeks. Participants will have regular visits for monitoring body weight, blood pressure, and blood tests to measure hormones such as ghrelin. Researchers will track changes in these measures to assess the impact of the different withdrawal methods. The total study duration includes 32 weeks of follow-up after treatment cessation to evaluate recovery and cardiometabolic changes following semaglutide withdrawal.

CONDITIONS

Brief Title

Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: Recovery Effects After Semaglutide Termination

Who Can Participate

Age: 18Years - 75Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Men and women with BMI 30 kg/m2 or higher, or BMI 27 kg/m2 or higher with related health issues like osteoarthritis, liver disease, sleep apnea, or hypertension
  • No pre-existing cardiovascular disease or type 2 diabetes
  • Age between 18 and 75 years inclusive
  • Currently receiving weekly semaglutide injections at a minimum dose of 1 mg with documented weight loss of at least 10% of pre-treatment body weight
  • Stable weight for the past 12 weeks with less than 5% change (self-reported)
  • Ability to read and understand English
Not Eligible

You will not qualify if you...

  • History of cardiovascular disease such as heart attack, stroke, or symptomatic peripheral arterial disease
  • Currently pregnant or breastfeeding
  • Diagnosed type 2 diabetes
  • Use of other weight-loss medications
  • Previous weight-loss surgery like gastric bypass or band
  • History of eating disorder
  • Severe kidney dysfunction (eGFR less than 25 ml/min)
  • Heart failure classified as New York Heart Association class II-IV
  • Significant liver disease or liver enzyme levels more than 2.5 times normal
  • Cancer needing chemotherapy, surgery, radiation, or palliative care within last 5 years (except basal cell skin cancer)
  • Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
  • Any other factor that may limit study adherence as judged by investigators

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - 16 weeks

Participants will either gradually reduce their semaglutide dosage by 25% every 4 weeks until complete cessation at week 16, or stop semaglutide treatment abruptly at week 16.

Visits approximately every 4 weeks during dose reduction period

Follow-up

Duration - 16 weeks

Participants are monitored for changes in body weight, blood pressure, and hormone levels after stopping semaglutide treatment.

Visits for assessments up to Week 32

Trial Site Locations

Total: 1 location

1

Leadership Sinai Centre for Diabetes

Toronto, Ontario, Canada, M5T 3L9

Actively Recruiting

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Research Team

C

Caroline K Kramer, MD PhD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

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