GLP-1 tachyphylaxis

Definition

Diminishing weight-loss response with continued GLP-1 exposure at a stable dose — a form of pharmacological tolerance. Documented in rodent models and clinically suspected in the ~20% of long-term users who plateau before reaching their goal weight despite continued dosing. Postulated mechanism: GLP-1 receptor downregulation or β-arrestin-mediated desensitization. Microdosing protocols and drug holidays have been proposed to mitigate it, but no randomized data exist.

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Definition curated by Weight Loss Rankings — sourced from FDA labels and peer-reviewed PubMed literature, never AI-generated summaries.

Related terms in Mechanism

• GLP-1 receptor
• GIP receptor
• Dual agonist
• Gastric emptying
• Food noise
• Triple agonist
• Amylin
• Non-peptide GLP-1 agonist
• A1C (glycated hemoglobin)
• MASH / MASLD

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