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

NCT07294950 | Recruiting Phase 3

• 1 other identifier: REB#1360
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Obesity (Disorder); Weight Change; Blood Pressure Monitoring; Appetite Regulation

Keywords

Randomized controlled trial; Interventional

Outcome Measures

Primary Outcomes (1)

• Differences in changes in body weight between each study group

  Differences in body weight change (%) between baseline visit 1 (semaglutide discontinuation) and 5 (16-weeks after complete semaglutide withdrawal) will be compared between the study groups

  32 weeks

Secondary Outcomes (2)

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

  32 weeks

• Differences in fasting ghrelin between each study group

  32 weeks

Other Outcomes (2)

• Changes in body mass index (BMI)

  32 weeks

• Changes in waist circumference

  32 weeks

Study Arms (2)

Gradual dose reduction of semaglutide

EXPERIMENTAL

Participants will reduce semaglutide dosage by 25% every 4-weeks until complete treatment cessation at week 16

Drug: Gradual dose reduction of semaglutide

Cessation of semaglutide

ACTIVE COMPARATOR

Participants will discontinue treatment at once at week 16

Drug: Abrupt cessation of semaglutide

Interventions

Gradual dose reduction of semaglutide DRUG

Pparticipants will reduce semaglutide dosage by 25% every 4-weeks until complete treatment cessation at week 16

Gradual dose reduction of semaglutide

Abrupt cessation of semaglutide DRUG

Cessation of semaglutide at 16-weeks

Cessation of semaglutide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead
• Heart and Stroke Foundation of Canada: collaborator

Study Sites (1)

Leadership Sinai Centre for Diabetes

Toronto, Ontario, M5T 3L9, Canada

RECRUITING

MeSH Terms

Conditions

Obesity; Body Weight Changes

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Caroline K Kramer, MD PhD

CONTACT

+1 4165864800 ext 7628; caroline.kramer@sinaihealth.ca

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: December 19, 2025
• Study Start: February 1, 2026
• Primary Completion (Estimated): September 1, 2028
• Study Completion (Estimated): May 1, 2029
• Last Updated: February 11, 2026

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)