Continued vs withdrawn semaglutide for weight maintenance: STEP-4
Withdrawal trial demonstrating that GLP-1 obesity therapy must be continued long-term to maintain weight loss. Discontinuation at week 20 led to substantial regain over the following 48 weeks.
Design
803 adults completed a 20-week run-in of semaglutide 2.4 mg, achieving a mean weight reduction of −10.6%. They were then randomized 2:1 to continued semaglutide or switched to placebo for an additional 48 weeks.
Outcome
Mean weight change from week 20 to week 68: −7.9% with continued semaglutide vs +6.9% with placebo switch. Roughly two thirds of the weight lost during the run-in was regained after withdrawal.
Clinical implication
Like antihypertensives or statins, GLP-1 obesity pharmacotherapy is most appropriately framed as chronic therapy. This shapes both insurance-coverage policy debates and patient counseling about expectations.