Weight Regain
The recovery of lost weight after discontinuing a weight management intervention. Weight regain after stopping GLP-1 receptor agonists is well-documented — most patients regain a significant portion of lost weight within 1-2 years of discontinuation, raising questions about the need for long-term treatment.
Technical Context
Weight regain after GLP-1 RA discontinuation reflects: restoration of pre-treatment appetite signalling (hypothalamic setpoint returns to baseline), metabolic adaptation (reduced basal metabolic rate from weight loss persists, creating positive energy balance when appetite returns), loss of pharmacological gastric emptying delay, and potentially, loss of central reward pathway modulation. STEP 4 data: participants who discontinued semaglutide 2.4mg after 20 weeks regained approximately 2/3 of lost weight over 48 weeks off treatment. STEP 1 extension: participants maintaining semaglutide 2.4mg for 2 years sustained ~15% weight loss; those discontinuing at 1 year regained substantially. These data support the chronic disease model — obesity, like hypertension, requires ongoing treatment for maintained benefit. The durability question has implications for healthcare economics, patient expectations, and long-term treatment planning.