STEP-4 (Wegovy, JAMA 2021) randomized patients who had completed 20 weeks of titration to either continue or switch to placebo. The continuation group lost an additional 7.9% over the next 48 weeks. The switched-to-placebo group regained 6.9% over the same period — netting roughly two-thirds of the original loss back.
SURMOUNT-4 (tirzepatide, JAMA 2024) showed similar regain on discontinuation.
The clinical interpretation: obesity is a chronic, relapsing condition. GLP-1 medications are not a "cure" — they are a long-term management tool. Modern obesity medicine treats them similarly to antihypertensives: indefinite use is appropriate when benefit-risk favors continuation.
If cost or side effects force discontinuation, a slow taper combined with structured lifestyle support reduces regain compared to abrupt stopping.