Overview
Peptide YY (PYY) is a 36-amino acid endogenous gut hormone released from L-cells of the distal intestine in proportion to caloric intake. PYY acts as a potent satiety signal, suppressing appetite through Y2 receptor activity in the hypothalamus. It is co-released with GLP-1 following meals, and the two hormones have complementary and sometimes synergistic appetite-suppressing effects. PYY is being explored as a weight loss therapeutic alongside or as an alternative to GLP-1 receptor agonists.
Mechanism of action
PYY exerts its primary satiety effect through binding to neuropeptide Y (NPY) Y2 receptors in the arcuate nucleus of the hypothalamus. Y2 receptor activation inhibits NPY/AgRP orexigenic neurons, reducing the drive to eat. The predominant circulating form PYY3-36 (generated by dipeptidyl peptidase-IV cleavage of PYY1-36) is highly selective for Y2 over Y1 receptors, making it more potent as a satiety signal with fewer peripheral effects. PYY also slows gastric emptying via the 'ileal brake' mechanism — reducing GI motility to optimize nutrient absorption. Peripheral PYY crosses the blood-brain barrier via active transport and acts directly on brainstem areas including the nucleus tractus solitarius. When co-administered with GLP-1, additive or synergistic appetite suppression has been observed without additional GI adverse events.
Dosing protocols
| Purpose | Route | Dosage | Frequency | Notes |
|---|---|---|---|---|
| Appetite suppression (IV infusion, research setting) | intravenous | 0.3–0.8 pmol/kg/min | acute infusion over 90-120 minutes | Research protocol only. Higher doses associated with nausea. No validated subcutaneous human protocol established. |
Dosing information is for educational purposes only. Consult a qualified healthcare professional before using any peptide.
Research summary
Human trials of intranasal PYY3-36 produced inconsistent appetite suppression, partly due to nausea at effective doses. IV infusion studies consistently show reduced ad libitum food intake (15-30%). Combined PYY3-36 and GLP-1 infusion (0.4 pmol/kg/min each) achieved a 27% reduction in energy intake in lean subjects. Cagrilintide (amylin analog) combined with semaglutide (FLOW trial) suggests that multi-hormone approaches to satiety are a viable strategy, positioning PYY combination therapies as next-generation anti-obesity candidates. PYY levels are chronically low in obese individuals and elevated after bariatric surgery, suggesting it contributes to post-surgical weight loss.
Side effects
Side effects vary by individual. This is not an exhaustive list. Report unusual symptoms to a healthcare professional.
Common stacks
Peptides commonly paired with Peptide YY for synergistic effects.
Legal status
No FDA-approved PYY therapeutic exists as of 2026. PYY analogs are in active pharmaceutical development. Research use only for synthetic forms.
Where to get it
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