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Mechanism Comparison: Anatomical vs Pharmacological Restriction
Gastric sleeve works through three simultaneous mechanisms: (1) volume restriction. The resected stomach holds 150–200mL vs 1,000mL pre-surgery, forcing smaller meals; (2) ghrelin suppression. Removal of the gastric fundus eliminates 70–85% of ghrelin-producin
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- Gastric sleeve works through three simultaneous mechanisms: (1) volume restriction. The resected stomach holds 150–200mL vs 1,000mL pre-surgery, forcing smaller meals; (2) ghrelin suppression. Removal of the gastric fundus eliminates 70–85% of ghrelin-producing cells, reducing hunger signaling; (3) accelerated gastric emptying into the small intestine, which triggers earlier GLP-1 release from L-cells in the ileum. These changes are immediate and permanent. There is no pharmacological washout period because the intervention is structural.
- GLP-1 receptor agonists like semaglutide (Wegovy, Ozempic) and tirzepatide (Mounjaro, Zepbound) mimic endogenous incretin hormones that regulate postprandial glucose and appetite. Semaglutide is a selective GLP-1 agonist; tirzepatide is a dual GIP/GLP-1 agonist with higher receptor affinity at both targets. Both slow gastric emptying by 30–50%, extending the window of elevated satiety hormones (GLP-1, PYY) and delaying the ghrelin rebound that normally triggers hunger 90–120 minutes after eating. The appetite suppression is downstream of gastric delay. Not a direct central nervous system effect. Semaglutide has a half-life of approximately 7 days; tirzepatide approximately 5 days. Weekly dosing maintains therapeutic plasma levels, but cessation means clearance within 4–6 weeks and return of baseline appetite signaling.
- The critical difference: sleeve creates forced compliance through anatomy. Overeating post-sleeve triggers nausea, vomiting, or dumping syndrome. Negative reinforcement that conditions smaller portions. Peptides require adherence. Missing doses during titration causes temporary appetite return. Discontinuation after goal weight triggers physiological rebound in most patients.