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Description
Theoretical concern: With many medications, the body adapts and effects diminish This is called tolerance or tachyphylaxis With semaglutide: Clinically significant tolerance does not appear to develop Appetite suppression persists with ongoing use Weight loss is maintained, not progressively reversing No evidence that higher doses are needed over time Some adaptation occurs: GI side effects often diminish (positive adaptation) Some patients report slightly less appetite suppression over years However, this doesnt appear to cause significant weight regain Blood Sugar Control Long-term glucose management: HbA1c improvements are maintained with continued use Some evidence suggests ongoing beta cell preservation Glucose control doesnt deteriorate while on medication Natural diabetes progression: Type 2 diabetes often progresses over time regardless of treatment Some patients may eventually need additional medications This reflects disease progression, not medication failure Cardiovascular Protection Ongoing benefits: SELECT trial showed continued protection over 3+ years No evidence of diminishing cardiovascular benefit Longer use associated with accumulated protection When Might Stopping Be Appropriate

Long-acting formulations have substantially longer half-lives due to modifications that slow absorption and degradation
DOZA , GLP-1, GIP -24.2% GLP-1 Phase 2 2-8C 24/7 ALLUVI SYNEDICA - TRIUMPH Phase 3 2 147 DOZA DOZA DOZA Telegram 2-8C

The clinician retains sole discretion to prescribe

doi: 10.1111/j.1464-5491.2012.03579.x

[DOI] [PubMed] [Google Scholar] 5.Mehdi SF, Pusapati S, Anwar MS, Lohana D, Kumar P, Nandula SA, et al
