NCT07294950

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.

• Status: Recruiting
• Phase: Phase 3
• Study type: Interventional
• Enrollment: 98 (estimated)
• Sponsor: Mount Sinai Hospital, Canada · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

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.

Detailed description

It is known that semaglutide induces a supra-physiologic agonism of GLP-1 receptors on central nervous system receptors associated with hedonic eating which likely promotes a homeostatic response (i.e. adaptation) related to appetite control. This concept raises the question of whether a gradual de-escalation of GLP-1RA could ameliorate the tendency for weight regain/cardiometabolic deterioration and compensatory changes in energy balance regulation following cessation of treatment.Thus, the investigators propose an open-label, parallel-arm, randomized controlled trial to determine whether a gradual dose reduction in semaglutide prior to complete discontinuation is associated with differential changes in weight and cardiometabolic profile (blood pressure homeostasis and energy balance regulatory hormones) as compared to immediate treatment cessation in individuals living with obesity without pre-existing cardiovascular disease who are receiving semaglutide for weight management.

Conditions

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

Interventions

Type	Name	Description
DRUG	Gradual dose reduction of semaglutide	Pparticipants will reduce semaglutide dosage by 25% every 4-weeks until complete treatment cessation at week 16
DRUG	Abrupt cessation of semaglutide	Cessation of semaglutide at 16-weeks

Timeline

• Start date: 2026-02-01
• Primary completion: 2028-09-01
• Completion: 2029-05-01
• First posted: 2025-12-19
• Last updated: 2026-02-11

Locations

1 site across 1 country: Canada