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.
Mount Sinai Hospital, Canada
98 participants
Feb 1, 2026
INTERVENTIONAL
Conditions
Summary
Semaglutide is a medication from the class of drugs called glucagon-like peptide-1 agonists that promote weight loss. There is little clinical data on the best strategy to achieve weight maintenance following weight reduction induced by semaglutide. For people who need to discontinue treatment, it is unknown whether the weight regain, its accompanied health benefits could be ameliorated with a gradual reduction in semaglutide. The investigators will study if a gradual reduction of semaglutide is associated with different heart risk profile and hormones involved in energy regulation as compared to immediate treatment cessation.
Eligibility
Inclusion Criteria5
- 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 Criteria12
- 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
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Interventions
Pparticipants will reduce semaglutide dosage by 25% every 4-weeks until complete treatment cessation at week 16
Cessation of semaglutide at 16-weeks
Locations(1)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07294950