GLP-1 tachyphylaxis
How GLP-1 receptor agonists work — receptors, gastric emptying, and the satiety pathway.
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
- TBWL (Total Body Weight Loss)
- C-peptide
- eGFR (estimated glomerular filtration rate)
- Visceral adipose tissue (VAT)
- AHI (apnea-hypopnea index)
- SNAC (oral semaglutide absorption enhancer)
Looking for more depth?
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- Browse the full GLP-1 glossary (124 terms across 8 categories)
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