REST trial opens to test tapering semaglutide versus stopping abruptly
The first randomized test of tapering semaglutide instead of stopping it is now enrolling, but results are not expected until 2029.
In February 2026, a research team at Mount Sinai Hospital in Toronto began recruiting for REST, short for Recovery Effects after Semaglutide Termination [1]. The trial, registered as NCT07294950, is designed to compare gradual dose reduction of semaglutide against stopping the drug abruptly [1][2]. Semaglutide is the molecule in Ozempic, Wegovy and Rybelsus.
REST is a randomized controlled trial [2]. It is enrolling adults living with obesity who do not have preexisting cardiovascular disease and who are taking semaglutide for weight management [2]. To qualify, participants must have already lost at least 10% of their body weight and had no further weight loss over the previous 12 weeks [2]. They are assigned at random to either a gradual dose reduction over 16 weeks or immediate treatment cessation [2].
The primary outcome is the difference in body weight change, measured as a percentage, between the two groups [2]. Secondary outcomes are 24-hour ambulatory blood pressure and fasting ghrelin levels [2]. Ghrelin is a hormone involved in appetite and energy balance. The published protocol, by Yevusiak and colleagues, states the researchers' hypothesis that gradual reduction will be associated with less weight regain and less cardiometabolic deterioration than immediate cessation [2].
That question is open because the protocol notes most people regain weight after semaglutide is abruptly withdrawn, and the drug's beneficial effects on cardiometabolic risk factors reverse along with it [2]. Whether stepping the dose down first changes either outcome has not been established in a randomized comparison [2].
The registry entry and the protocol list a completion date of May 2029 [1]. The number of participants the trial aims to enroll has not been reported, and no enrollment target appears in the registry entry or the protocol [1][2].
Why it matters for patients
Stopping semaglutide is a common point of decision for people who take it for weight management, and the protocol's own background section describes what usually follows abrupt withdrawal: weight comes back and cardiometabolic gains reverse [2]. REST is set up to test whether the way the drug is stopped changes that, but it is testing the question rather than answering it. Until it reports, the comparison between tapering and stopping has not been settled by a randomized trial [2].
The design also sets boundaries on what the results will describe. Participants must have lost at least 10% of body weight and plateaued before enrolling, so the findings will apply to that group rather than to everyone who takes the drug [2]. People with preexisting cardiovascular disease are excluded [2]. The trial studies semaglutide only; it will not produce findings about tirzepatide (Mounjaro, Zepbound) or orforglipron (Foundayo).
What happens next
Recruitment began in February 2026 [1]. The trial's listed completion date is May 2029 [1]. No results have been posted, and no interim findings from REST have been reported [1].
Sources
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