Peptide YY (3-36)

Summary

Peptide YY (3-36) [PYY(3-36)] is an endogenous truncated form of PYY released postprandially from L-cells of the distal gut. It is the predominant circulating form of PYY and acts as a potent anorectic agent via preferential Y2 receptor agonism. It has been investigated as a pharmacological target for obesity treatment, with multiple clinical trials exploring intranasal, subcutaneous, and combination formulations.

Mechanism of Action

Selective agonist of the Y2 receptor (NPY2R) in the hypothalamic arcuate nucleus; inhibits neuropeptide Y (NPY) neurons, reducing food intake and promoting satiety. Also slows gastric emptying and reduces gastrointestinal motility via peripheral Y2 receptors.

Routes of Administration

Goals & Uses

• Post-bariatric surgery gut hormone modulationMetabolic / SurgicalLow
• Type 2 diabetes / glycemic controlMetabolic / EndocrineLow
• Appetite suppression / Reduction of food intakeMetabolic / ObesityModerate
• Weight loss in obesityMetabolic / ObesityModerate

Contraindications

• PregnancyPopulationHighPotential fetal risk or insufficient safety data
• Severe gastrointestinal dysmotilityGastrointestinalModerate
• Eating disorders (anorexia nervosa)Psychiatric / NutritionalHigh

Adverse Effects

• Injection site reactionsLocalUncommon
• HeadacheNeurologicUncommonPain in the head or upper neck
• Dizziness / lightheadednessNeurologicUncommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• VomitingGastrointestinalUncommonForceful expulsion of stomach contents
• Nasal irritation / epistaxisLocal / NasalUncommon

Drug Interactions

• Oxyntomodulin / GLP-1/glucagon dual agonistsLow
• GLP-1 receptor agonists (e.g., liraglutide, semaglutide)Moderate
• Opioid analgesicsModerate

Population Constraints

• Pediatric patientsAgeRelative
• Breastfeeding womenReproductiveRelative
• Patients with renal impairmentOrgan ImpairmentRelative
• Elderly patientsAgeRelative

Regulatory Status

• European UnionInvestigationalNo EMA marketing authorization; clinical trials conducted within EU member states.
• United StatesInvestigationalInvestigated under IND regulations; no FDA approval. Studied in obesity-related clinical trials.
• United KingdomInvestigationalNo MHRA approval; research ongoing at institutions including Imperial College London.

Not approved by FDA, EMA, or MHRA for any indication. Investigated in Phase I and Phase II clinical trials for obesity. No approved therapeutic product exists as of 2024.

Evidence & Sources

No sources recorded yet.