PYY

PYY is a hormone your gut releases after you eat. Its active form, called PYY3-36, is one of the signals that tells the brain a meal has arrived and that it is time to stop eating. The amount released tracks how many calories the meal contained, which is why it is described as a fullness signal. Researchers have given PYY3-36 to people through a drip to see whether adding more of it makes people eat less. It is not an approved medicine anywhere, and nothing containing it can be prescribed.

In short studies where PYY3-36 was dripped into a vein, people ate noticeably less at a meal offered afterwards, and this happened in people with obesity as well as in lean people. Those studies measured how much someone ate over a single day. They did not measure weight change over weeks or months, so they show an effect on appetite rather than an effect on body weight. When another research group tried to repeat the original animal experiments, they could not get the same result, which became a long-running disagreement in the field. More recently, a longer-acting version was designed so it could be given as a regular injection instead of a drip, and it was tested on top of an existing weight-loss medicine. The added benefit was small enough that the researchers running it described it as not clinically meaningful, stomach-related side effects were common, and the higher dose was not tolerated well enough to continue.

Not FDA-approved for any indication, and no PYY product of any kind is approved anywhere. Exogenous PYY3-36 has been given to humans only in research settings, and the modern long-acting analogue tested alongside semaglutide produced a treatment effect its own investigators described as not clinically meaningful, with poor tolerability at the higher dose. WADA status: PYY, PYY3-36 and peptide YY are not named anywhere on the 2026 WADA Prohibited List (checked directly against the list text, 2026-09-10). Because S0 (Non-Approved Substances) captures any pharmacological substance not addressed elsewhere on the List and with no current approval by any governmental regulatory health authority for human therapeutic use, an unapproved PYY3-36 preparation falls under S0 by default. Not DEA-scheduled.

No PYY product is approved anywhere, so nothing containing it has been reviewed for safety or quality by a regulator. In research, stomach and bowel side effects such as nausea have been the common and dose-limiting problem. PYY itself is not named on the banned list for drug-tested sport, but anything not approved as a medicine anywhere is off-limits in drug-tested sport by default. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ PYY is not an approved medicine in any country and no PYY product has been reviewed by a regulator for safety, quality, or effectiveness. Information in this entry is informational, not medical advice.

⚠️ What this entry covers, and what it does not. This entry is about exogenous PYY3-36 — PYY given to people as an intervention. PYY is also an extensively studied piece of normal human physiology: it rises after meals, it rises sharply after bariatric surgery, and it shifts with dietary fibre. That endogenous literature measures PYY as a marker of something else happening and does not establish anything about administering PYY. Findings of the "PYY levels rose after X" kind are outside this entry's scope and are not evidence that taking PYY does anything.

⚠️ An appetite effect measured over one day is not a weight-loss result. The human infusion studies below measured how much people ate at a test meal and across 24 hours. They did not run long enough to measure weight. The one program that did test a PYY analogue for weight management over months reported an effect its own investigators called not clinically meaningful.

PYY (peptide YY, sometimes written peptide tyrosine tyrosine) is a hormone released from the gastrointestinal tract after eating, in proportion to the calorie content of the meal.[¹] The circulating form relevant to appetite research is the cleaved fragment PYY3-36, which is an agonist at the neuropeptide Y Y2 receptor.[¹]

Mechanism. The Y2 receptor is a presynaptic inhibitory receptor expressed on neuropeptide Y (NPY) neurons in the arcuate nucleus of the hypothalamus, a region accessible to hormones circulating in the blood.[¹] The 2002 Nature report that established the mechanism found that PYY3-36 inhibits the electrical activity of NPY nerve terminals, which in turn activates neighbouring pro-opiomelanocortin (POMC) neurons — the same POMC step that sits upstream of the melanocortin pathway described in [setmelanotide.md](./setmelanotide.md).[¹] In mice lacking the Y2 receptor, the appetite effect did not occur, which is the evidence that the effect runs through Y2R rather than around it.[¹]

The human infusion findings. Two reports form the human basis for the appetite claim, and both are acute studies:

- The 2002 Nature paper — predominantly a rodent study — included a human component in which infusion of PYY3-36 at normal postprandial concentrations decreased appetite and reduced food intake by 33% over 24 hours.[¹] - The 2003 New England Journal of Medicine report was a double-blind, placebo-controlled crossover study in 12 people with obesity and 12 lean people. Caloric intake at a buffet lunch offered two hours after infusion fell by 30% in the obese participants and 31% in the lean participants, and cumulative 24-hour caloric intake fell in both groups.[²] The same paper reported that endogenous fasting and postprandial PYY levels were lower in the obese participants, and that fasting PYY correlated negatively with body-mass index.[²]

The framing that paper argued for is worth stating precisely, because it is often reported loosely: its finding was that people with obesity are not resistant to the appetite effect of PYY, in contrast to the leptin resistance described in [metreleptin.md](./metreleptin.md).[²] That is a statement about responsiveness in a two-hour window in 24 people. It is not a statement about weight loss.

The replication dispute. In 2004, a separate group published a Brief Communications Arising item in Nature reporting that they had been unable to replicate the rodent food-intake results, and argued that the difficulty of replication called into question the value of an anti-obesity approach based on administering PYY3-36.[³] The dispute concerned the rodent experiments. It is recorded here because the field's subsequent caution is not fully legible without it.

What happened when it was developed as a drug. The most informative modern source is a 2025 report in Obesity covering a long-acting PYY3-36 analogue (PYY1875) from preclinical work through Phase 1 and Phase 2 studies.[⁴] In obese male rats, the analogue added weight loss on top of semaglutide.[⁴] In the Phase 1 study, all doses alone and with semaglutide were tolerated.[⁴] In the Phase 2 study, the treatment effect of PYY1875 versus placebo as an add-on to semaglutide was described by the investigators as "modest but not clinically meaningful"; gastrointestinal adverse events were common at that dose, and the dose-escalation regimen was not tolerated.[⁴] The authors' own summary is that the analogue "showed modest efficacy as an add-on to semaglutide for weight management in people with obesity, but the treatment was not well tolerated."[⁴]

Regulatory status (US). No PYY product is FDA-approved for any indication, and a search of FDA labeling records for peptide YY returns no result (checked 2026-09-10). Not DEA-scheduled.

Regulatory status (sport — WADA). PYY, PYY3-36 and peptide YY are not named anywhere on the 2026 WADA Prohibited List (checked directly against the list text, 2026-09-10). That absence does not make it permitted. S0 (Non-Approved Substances) covers, verbatim, any pharmacological substance "which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development or discontinued, designer drugs, substances approved only for veterinary use)" — which describes an unapproved PYY3-36 preparation exactly. Substances in S0 are Specified Substances and are prohibited at all times. Athletes should verify current status with their National Anti-Doping Organization.

Commonly reported

• Gastrointestinal adverse events — common at the analogue dose given with semaglutide, and the reason the escalation regimen was not tolerated.[⁴]

No approved product exists. Anything sold as PYY or PYY3-36 is outside any regulatory system for identity, purity, dose accuracy, or sterility.

The route studied is not the route available. Human efficacy data come from intravenous infusion in supervised research settings. Nothing in this entry supports subcutaneous self-administration.

Pregnancy and lactation: no data. Default to contraindicated.

Drug-tested athletes: captured by WADA S0 by default as an unapproved substance — see the regulatory note above.

Gut hormone

A chemical messenger released by the digestive tract that travels in the blood and reports back to the brain about food that has been eaten.

PYY3-36

The shortened, active form of PYY that the body makes from the full hormone. It is the form used in appetite research.

Y2 receptor

The docking point in the brain that PYY3-36 fits into. Switching it on turns down the signals that drive hunger.

Infusion

Giving something slowly into a vein through a drip, rather than as an injection under the skin.

Analogue

A lab-made version of a natural substance, redesigned so it lasts longer in the body or is easier to give.

1. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR. (2002). Gut hormone PYY(3-36) physiologically inhibits food intake. Nature, 418(6898):650–654.(PMID 12167864)
2. Batterham RL, Cohen MA, Ellis SM, Le Roux CW, Withers DJ, Frost GS, Ghatei MA, Bloom SR. (2003). Inhibition of food intake in obese subjects by peptide YY3-36. New England Journal of Medicine, 349(10):941–948.(PMID 12954742)
3. Tschöp M, Castañeda TR, Joost HG, Thöne-Reineke C, Ortmann S, Klaus S, Hagan MM, Chandler PC, Oswald KD, Benoit SC, Seeley RJ, Kinzig KP. (2004). Physiology: does gut hormone PYY3-36 decrease food intake in rodents? Nature, 430(6996):1 p following 165; discussion 2 p following 165.(PMID 15243972)
4. Wulff BS, Chambers AP, Osorto Contreras CK, Kirkeby K, Rinnov AR, Sustarsic RK, Østergaard S, Laabs JE, et al. (2025). Long-acting PYY3-36 analogue with semaglutide for obesity: from preclinical assessment through randomized clinical studies. Obesity (Silver Spring), 33(8):1457–1474.(PMID 40629530)

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