REST

RecruitingPhase 3

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

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

Lead sponsor

Mount Sinai Hospital, Canada

Asset

Semaglutide

GLP-1 agonist

Listed sites

Recruiting sites

Enrollment

estimated

Study population

Obesity / overweight

Key I/E criterion

•BMI ≥30

Primary endpoint

•Body weight, % change

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07294950

Org study IDREB#1360

Timeline

Milestones

Study first posted2025-12-19actual

Study start2026-02-01actual

Last update posted2026-02-11actual

Primary completion2028-09estimated (month precision)

Study completion2029-05estimated (month precision)

Assets

Investigational agents

Semaglutide

Study populations

Who this study enrolls

Obesity / overweight

Eligibility

Who can enroll

Minimum age18 Years

Maximum age75 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Men and women with previously diagnosed BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and adiposity-related complications (such as osteoarthritis, nonalcoholic liver disease, sleep apnea, and hypertension) without preexisting cardiovascular disease or type 2 diabetes.

•Age 18 - 75 years inclusive

•Ongoing weight-loss treatment consisting of weekly subcutaneous semaglutide at minimum dose of 1 mg/weekly with documented weight reduction of at least 10% of pre-treatment body weight

•Stable weight over past 12 weeks (less than 5% change in body weight) (self-reported)

•Ability to read and understand English

Exclusion criteria

•Previously diagnosed cardiovascular disease defined as previous myocardial infarction, previous stroke, or symptomatic peripheral arterial disease.

•Currently pregnant or lactating

•Previously diagnosed type 2 diabetes

•Use of any other pharmacological treatment for weight-loss

•Previous surgical treatment for weight loss such as gastric bypass or gastric band

•Any history of eating disorder

•Renal dysfunction as evidenced by estimated glomerular filtration rate < 25 ml/min by CKD-EPI Creatinine Equation

•New York Heart Association class II-IV heart failure

•Hepatic disease considered to be clinically significant (includes jaundice, chronic hepatitis, or previous liver transplant) or transaminases >2.5X the upper limit of normal

•Malignant neoplasm requiring chemotherapy, surgery, radiation or palliative therapy within the previous 5 years (with the exception of basal cell skin cancer)

•Personal or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2

•Any other factor likely to limit adherence to the study, in the opinion of the investigators

Endpoints (5)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Weight & body composition

Cardiometabolic biomarkers

Weight & body composition

3 endpoints

Primary/protocol endpoint

Differences in changes in body weight between each study group

Time frame:32 weeks

Body weight, % change

percent change from baseline, improvement

Other/protocol endpoint

Changes in body mass index (BMI)

Time frame:32 weeks

BMI, change

change from baseline, improvement

Other/protocol endpoint

Changes in waist circumference

Time frame:32 weeks

Waist circumference, change

change from baseline, improvement

Cardiometabolic biomarkers

2 endpoints

Secondary/protocol endpoint

Differences in 24-h systolic BP levels between each study group

Time frame:32 weeks

Systolic BP, change

change from baseline, improvement

LOINC 8480-6

Secondary/protocol endpoint/low confidence

Differences in fasting ghrelin between each study group

Time frame:32 weeks

change from baseline, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 1, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.