Withdrawal Effect
Symptoms that occur when a drug is discontinued after prolonged use, caused by the body's physiological adaptation to the drug's presence. For peptide drugs like GLP-1 receptor agonists, weight regain after discontinuation is a form of withdrawal from the drug's appetite-suppressing effects.
Technical Context
Peptide drug withdrawal is generally not associated with the classical physical withdrawal syndromes seen with opioids, benzodiazepines, or alcohol (because peptide drugs don't typically cause physical dependence). However, disease-related withdrawal effects occur: GLP-1 RA discontinuation leads to weight regain in 50-70% of patients within 1-2 years (STEP 4 extension data showed approximately 2/3 of weight lost was regained after stopping semaglutide); GH replacement discontinuation causes return of GH deficiency symptoms (increased visceral fat, decreased lean mass, fatigue, reduced quality of life); and GnRH agonist discontinuation restores the hormonal milieu that was therapeutically suppressed. These withdrawal effects reflect reversal of pharmacological effects rather than true pharmacological dependence.