Peptide YY
The fullness hormone that works when infused for hours and has never become a medicine
PYY is released by the gut after a meal in proportion to the calories eaten. Its shortened form, PYY3-36, suppresses appetite through a receptor in the hypothalamus. It has been infused into people many times, and it works best in combination with another gut hormone.
What is it?
PYY comes from the same family as neuropeptide Y and is released by intestinal L-cells in proportion to the calories in a meal. The enzyme DPP-4 trims it to PYY3-36, which acts on the Y2 receptor, a receptor sitting on the appetite-driving neurons of the arcuate nucleus.
The 2002 paper that put it on the map showed that injecting PYY3-36 reduced food intake in rats and in mice, and not in mice lacking the Y2 receptor, which is how the mechanism was established.
A long-acting analogue cut food intake by up to 55% in a phase 1 trial, at the cost of nausea. In people it has mostly been infused rather than injected at home, and the results are modest alone and better in company. A crossover study in 25 overweight men found no significant reduction in energy intake from PYY3-36 or GLP-1 given separately, and a reduction when the two were infused together. A separate study combining it with oxyntomodulin cut energy intake by 42.7% against saline.
The most recent drug attempt shows the problem. PYY1875, a long-acting analogue, added only a modest, not clinically meaningful effect to semaglutide 2.4 mg, and its higher dose was not tolerated because of gastrointestinal effects. Combination molecules such as GEP44, which joins GLP-1 and PYY activity, have so far only been reported in rodents.
It also slows the stomach, which is part of how satiety hormones work and part of why they cause nausea. After bariatric surgery, post-meal PYY rises sharply, but a meta-analysis found it does not explain why some people lose more weight after gastric bypass than others. It also behaves as a marker: high in anorexia nervosa and bile acid diarrhoea, low in obesity.
Mechanism of Action
PYY is released by intestinal L-cells after meals; its trimmed form PYY3-36 acts on Y2 receptors in the arcuate nucleus to reduce appetite.
Satiety via Y2
PYY3-36 reduces food intake through the Y2 receptor; mice lacking the receptor did not respond.
Slower stomach
It slows gastric emptying, part of satiety and part of why nausea limits the dose.
Gut fluid
PYY opposes cAMP-driven intestinal secretion, and its levels are altered in several diarrhoeal conditions.
Published Research
These are the studies in people, read from their PubMed abstracts: three infusion studies and the animal paper that established the mechanism.
Alone it did nothing; with GLP-1 it worked
In a randomised double-blind four-arm crossover study in 25 overweight men, infusing PYY3-36 alone changed energy intake by −4.2% (p = 0.8) and GLP-1 alone by −3.0% (p = 0.9). Only the two infused together reduced energy intake.
Additive with oxyntomodulin
In 12 overweight or obese volunteers in a randomised double-blind placebo-controlled study, infusing PYY3-36 together with oxyntomodulin cut energy intake at a test meal by 42.7% against saline, significantly more than either hormone alone.
It slows the stomach
In eight healthy adults given saline, PYY1-36 or PYY3-36 with a radiolabelled omelette, both forms slowed gastric emptying and PYY3-36 did so most: half-emptying time rose from 63.1 minutes on saline to 87.0 minutes.
A long-acting analogue, phase 1
In overweight and obese volunteers, the extended-release PYY analogue Y14 suited dosing every 7 to 14 days; multiple doses cut food intake by 38-55% and weight by 2.9-3.6 kg against placebo at 31 days, with nausea, vomiting and injection-site reactions the commonest effects.
Triple infusion with GLP-1 and oxyntomodulin
In obese people with prediabetes or type 2 diabetes, four weeks of infused GLP-1, oxyntomodulin and PYY (15 patients) cut weight by 4.4 kg against 2.5 kg on saline (11) and improved fructosamine and post-meal glucose.
No effect on reproductive hormones
In 18 healthy men, an 8-hour infusion of PYY3-36 (0.4 pmol/kg/min) left LH pulses, FSH and testosterone unchanged against vehicle.
PYY1875 on top of semaglutide
In phase 1 and 2 studies, a long-acting PYY3-36 analogue added to semaglutide 2.4 mg gave only a modest, not clinically meaningful extra effect at 1.0 mg; gastrointestinal events were common and the 2.0 mg escalation was not tolerated.
Predicting sleeve gastrectomy
After sleeve gastrectomy, post-meal PYY and GLP-1 peaks rose, and the preoperative PYY response and its increase after surgery predicted weight loss at 36 months.
After bypass: portions and BMI
In non-diabetic women after Roux-en-Y gastric bypass, fasting PYY correlated inversely with BMI at one year, and a larger post-meal rise went with smaller ideal portion sizes.
Exercise after bypass
After gastric bypass, PYY and GLP-1 rose after exercise following a meal, which they had not done before surgery; the PYY area under the curve went from 9.9 to 224.2.
Raised in bile acid diarrhoea
People with bile acid diarrhoea had higher fasting PYY than controls, which fell with sequestrant or liraglutide treatment and tracked bile acid markers.
Low in familial GUCY2C diarrhoea
Patients with familial GUCY2C diarrhoea syndrome had about half the density of PYY-containing cells in the terminal ileum (25.3 against 48.1 per mm²) and lower PYY gene expression.
Anorexia nervosa and obesity in girls
Serum PYY was highest in girls with anorexia nervosa (77.2 pg/mL), lowest in obesity (36.0) and intermediate in controls (49.7), with a strong inverse correlation with BMI.
Stress and smoking
In smokers trying to quit and non-smokers, early life adversity was associated with lower PYY, with no consistent effect of nicotine addiction or relapse.
The paper that established the mechanism
Peripheral PYY3-36 reduced food intake and weight gain in rats, and reduced food intake in mice but not in mice lacking the Y2 receptor, showing the effect runs through that receptor. It also changed activity in the arcuate nucleus and lowered hypothalamic NPY messenger RNA.
Not why gastric bypass varies
Pooling 5 studies of 181 patients, fasting and post-meal PYY were the same in good and poor responders to Roux-en-Y gastric bypass, and no PYY gene variants predicted weight loss.
GLP-1 and PYY in one molecule
A review of GEP44, a GLP-1 and PYY dual agonist, reports rodent data showing lower food intake and body weight than single GLP-1 drugs, with better gastrointestinal tolerability; it has not been tested in people.
Dosing Data
There is no approved PYY drug. Human studies have used short intravenous infusions or injected long-acting analogues.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the infusion studies, which are short and supervised.
Contraindications & Cautions
Not a medicine.
Legal Status
PYY is not a medicine.
Frequently Asked Questions
?What does PYY do?
It is released by the gut after a meal in proportion to calories eaten, and its PYY3-36 form suppresses appetite through the Y2 receptor in the hypothalamus.
?Does it cause weight loss in people?
Infused alone it did not significantly reduce energy intake in 25 overweight men. Combined with GLP-1 or with oxyntomodulin it did, by up to 42.7% at a test meal.
?Why has it not become a drug?
It is short-lived, works best with another hormone, and causes nausea. The human work is hours-long infusions under supervision.
?How is it related to neuropeptide Y?
Same family, opposite job: neuropeptide Y in the brain drives feeding, while PYY from the gut suppresses it through a different receptor.
?Does PYY explain weight loss after bariatric surgery?
Partly at most. Post-meal PYY rises after surgery, and its response predicted weight loss after sleeve gastrectomy in one study, but a meta-analysis found PYY was the same in good and poor responders to gastric bypass.
?Can PYY be added to semaglutide?
A long-acting PYY analogue, PYY1875, was tested on top of semaglutide 2.4 mg and added only a modest, not clinically meaningful effect, with poor tolerability at the higher dose.
References
- [pubmed] Schmidt JB, et al. "Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure, and appetite in overweight men." Am J Physiol Endocrinol Metab, 2014;306(11):E1248-56. PMID: 24735885.
- [pubmed] Field BC, et al. "PYY3-36 and oxyntomodulin can be additive in their effect on food intake in overweight and obese humans." Diabetes, 2010;59(7):1635-9. PMID: 20357366.
- [pubmed] Witte AB, et al. "Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man." Regul Pept, 2009;158(1-3):57-62. PMID: 19651163.
- [pubmed] Batterham RL, et al. "Gut hormone PYY(3-36) physiologically inhibits food intake." Nature, 2002;418(6898):650-4. PMID: 12167864.
- [pubmed] Karra E, et al. "The role of gut hormones in the regulation of body weight and energy homeostasis." Mol Cell Endocrinol, 2010;316(2):120-8. PMID: 19563862.
- [clinical-trial] Tan TM, et al. "Safety and efficacy of an extended-release peptide YY analogue for obesity: A randomized, placebo-controlled, phase 1 trial." Diabetes Obes Metab, 2021;23(7):1471-1483. PMID: 33606914.
- [clinical-trial] Behary P, et al. "Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body Weight and Glycemia in Obesity and Prediabetes/Type 2 Diabetes: A Randomized, Single-Blinded, Placebo-Controlled Study." Diabetes Care, 2019;42(8):1446-1453. PMID: 31177183.
- [clinical-trial] Izzi-Engbeaya C, et al. "Effects of Peptide YY on the Hypothalamic-Pituitary-Gonadal Axis in Healthy Men." J Clin Endocrinol Metab, 2020;105(3):833-8. PMID: 31628465.
- [pubmed] Wulff BS, et al. "Long-acting PYY(3) (-36) analogue with semaglutide for obesity: from preclinical assessment through randomized clinical studies." Obesity (Silver Spring), 2025;33(8):1457-1474. PMID: 40629530.
- [pubmed] Macanhã Scremin G, et al. "Hormone PYY does not Explain the Variability in Weight Loss After Roux-en-Y Gastric Bypass: Evidence From a Meta-Analysis." Obes Surg, 2026;36(4):1946-1954. PMID: 41854997.
- [pubmed] Janot C, et al. "Meal-induced PYY and GLP1 secretions differently predict long-term weight loss after sleeve gastrectomy." Clin Nutr, 2025;54:202-209. PMID: 41092583.
- [pubmed] Andreoli MF, et al. "Associations of PYY, GLP-1 and LEAP2 with changes in feeding-related cognition, body weight and glucose homeostasis after bariatric surgery in non-diabetic women." J Neuroendocrinol, 2026;38(6):e70207. PMID: 42210737.
- [pubmed] Gil S, et al. "Roux-en-Y Gastric Bypass Improves Insulin Response and Secretion of GLP-1 and PYY in Response to Postprandial Acute Exercise." Obes Surg, 2025;35(12):4989-4999. PMID: 41238973.
- [pubmed] Lange AH, et al. "Circulating levels of PYY are increased in individuals with bile acid diarrhoea." J Clin Endocrinol Metab, 2026. PMID: 42496159.
- [pubmed] Mazzawi T, et al. "Low Small Intestinal PYY Immunoreactive Cell Density and PYY Gene Expression in Patients With Familial GUCY2C Diarrhea Syndrome." APMIS, 2026;134(3):e70173. PMID: 41736394.
- [pubmed] Gołąb-Jenerał K, et al. "Assessment of serum concentrations of the "satiety hormone" - peptide YY concentration in body weight disorders in girls with anorexia nervosa and obesity." Endokrynol Pol, 2026;77(1):72-80. PMID: 41712241.
- [pubmed] Miller AA, et al. "Nicotine addiction and the influence of life adversity and acute stress on PYY: Prediction of early smoking relapse." Pharmacol Res Perspect, 2024;12(5):e70016. PMID: 39315578.
- [pubmed] Burmeister MA, et al. "Glucagon-like peptide-1 and peptide YY multi-agonism with GEP44 to optimize weight loss and glycemic control while reducing gastrointestinal side effects: the future of anti-obesity pharmacotherapy?." Front Endocrinol (Lausanne), 2026;17:1925534. PMID: 42602523.
Sources & Citations
Studies were read from their PubMed abstracts; PYY has no label. Read October 7, 2026.
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