Recovery after stopping semaglutide: effects on weight, heart risk, and appetite
Impact of Semaglutide Withdrawal on Cardiometabolic Profile and Physiology of Energy Balance: a Randomized Controlled Trial Comparing Gradual Dose Reduction With Immediate Treatment Cessation.
This trial will test whether gradually lowering semaglutide instead of stopping it suddenly changes weight, heart risk markers, and appetite hormones in adults with obesity who lost at least 10% of their weight on semaglutide.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 98 (estimated) |
| Ages | 18 Years to 75 Years |
| Sex | All |
| Sponsor | Mount Sinai Hospital, Canada Academic / other |
| Drugs / interventions | chemotherapy, radiation |
| Locations | 1 site (Toronto, Ontario) |
| Trial ID | NCT07294950 on ClinicalTrials.gov |
What this trial studies
This open-label, parallel-arm randomized trial compares gradual dose reduction of weekly semaglutide to abrupt cessation in adults with obesity who achieved ≥10% weight loss on semaglutide. Participants aged 18–75 with BMI ≥30 kg/m2 (or ≥27 with adiposity-related complications) and without prior cardiovascular disease or type 2 diabetes will be randomized to a tapering protocol or immediate stop. Investigators will measure changes in body weight, blood pressure homeostasis, cardiometabolic markers, and hormones that regulate energy balance over the recovery period. The single-center study is led by Mount Sinai Hospital (Leadership Sinai Centre for Diabetes) in Toronto and requires clinic visits and blood testing to capture physiologic and hormonal responses.
Who should consider this trial
Good fit: Adults 18–75 with BMI ≥30 (or ≥27 with adiposity-related complications) who are on weekly semaglutide ≥1 mg, have lost at least 10% body weight, and have stable weight for 12 weeks without prior cardiovascular disease or type 2 diabetes.
Not a fit: People with prior cardiovascular disease, type 2 diabetes, current pregnancy or lactation, prior bariatric surgery, use of other weight-loss medications, or who did not achieve ≥10% weight loss on semaglutide are unlikely to match the study population and may not benefit.
Why it matters
Potential benefit: If successful, gradual dose reduction could reduce weight regain and help preserve cardiometabolic improvements after stopping semaglutide.
How similar studies have performed: Although GLP-1 receptor agonists like semaglutide reliably produce weight loss, there are limited clinical data on gradual de-escalation after stopping treatment, so this specific approach is largely untested.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Toronto, Ontario
- Leadership Sinai Centre for Diabetes — Toronto, Ontario, Canada (Recruiting)
Study contacts
- Study coordinator: Caroline K Kramer, MD PhD
- Email: caroline.kramer@sinaihealth.ca
- Phone: +1 4165864800 ext 7628
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.