Reduced food intake after infusion in humans [1]
The founding human finding: PYY3-36 infusion reduced caloric intake at a subsequent buffet meal in both lean and obese participants, with obese participants remaining responsive.
PrecisePep/Peptide Library/Peptide YY (PYY)
Metabolic & Adipose Regulation
Peptide YY (PYY)
PYY3-36 · peptide tyrosine tyrosine · PYY analogues
The satiety hormone the gut releases after a meal — a genuine target with a genuine development history, and a nasal formulation that failed on nausea so badly it defined the problem for the whole class.
00 Overview
PYY is one of the two hormones your gut releases when you finish eating. Intestinal L-cells secrete it alongside GLP-1 in proportion to caloric load, and the active form — PYY3-36, produced when DPP-IV clips the first two residues — acts on Y2 receptors in the arcuate nucleus to reduce appetite. It is a real, endogenous satiety signal, not a designed drug.
Interest surged after a 2002 report that PYY3-36 infusion reduced food intake in humans, and surged again when it emerged that bariatric surgery substantially elevates postprandial PYY — suggesting some of surgery's effect is hormonal rather than mechanical.[1][2]
Then it ran into the wall that defines this compound. An intranasal PYY3-36 programme was discontinued because the doses required for meaningful appetite reduction produced intolerable nausea and vomiting. The therapeutic window between satiety and emesis proved too narrow to build a drug in. That failure is why PYY analogues are now developed almost exclusively as combination partners with GLP-1 agonists, at doses low enough to be tolerated.[3]
Barely obtainable, and that is not an accident
PYY is unstable, has a half-life of minutes, and requires either infusion or a formulation nobody has made work outside a trial. It is largely absent from consumer grey-market channels for practical chemistry reasons rather than regulatory ones. Anything sold as consumer-grade PYY deserves a specific question about what it actually is and how it is meant to be delivered.
// Mechanism of action
Y2 receptor agonism in the arcuate nucleus. PYY3-36 acts on presynaptic inhibitory Y2 autoreceptors on NPY/AgRP neurons — the orexigenic population. Inhibiting the appetite-driving neurons reduces food intake, which is a different route from GLP-1's direct action on anorexigenic pathways.
Selectivity comes from the cleavage. Full-length PYY1-36 activates Y1, Y2 and Y5 receptors and is not selectively anorexigenic. DPP-IV cleavage to PYY3-36 confers Y2 selectivity — the same enzyme that degrades GLP-1 is what activates PYY.
Complementary to GLP-1 rather than overlapping. Both are L-cell products released together, acting on different receptors in overlapping circuitry. That is the argument for combining them and the reason the current development programmes do.
Slowed gastric emptying and the "ileal brake". PYY contributes to the feedback that slows transit when nutrients reach the distal intestine — part of the satiety effect and part of the nausea.
Why nausea is mechanistically inseparable. The circuitry mediating satiety overlaps substantially with that mediating nausea. This is the same problem GLP-1 agonists have; PYY has it more severely, with a narrower window between the two.
01 Reported benefits
Effects that have been reported. A study-tier entry means a result was published — not that the effect is established, reproducible, or transferable from a rodent to a person.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Elevated postprandial PYY after bariatric surgery [2]
Roux-en-Y gastric bypass and sleeve gastrectomy substantially increase postprandial PYY and GLP-1, and this hormonal shift is thought to contribute to the appetite changes surgery produces.
Intranasal programme discontinued on tolerability [3]
The most instructive result. Doses producing meaningful appetite reduction produced intolerable nausea and vomiting, and development did not proceed. The therapeutic window is the central problem with this target.
Y2-selective analogues in current development [4]
Long-acting Y2-selective analogues are in clinical development, generally as combination partners with GLP-1 agonists at doses chosen to stay below the nausea threshold rather than as monotherapy.
No consumer-grade formulation exists
Chemical instability, a minutes-long half-life and no validated delivery route outside trials mean there is no standardised consumer product. This is a practical statement rather than a regulatory one.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Additive satiety with GLP-1 agonists
Two L-cell hormones, two receptors, overlapping circuits — the same logic that motivates amylin plus incretin combinations. This is where the active development is, and it has not yet produced an approved product.
Improved insulin sensitivity via sustained caloric reduction
The proposed metabolic benefit runs through weight loss rather than through direct insulin signalling — an indirect route, and a longer one than the incretin case.
Reproducing part of the bariatric effect pharmacologically [2]
The most interesting hypothesis attached to this target. It also implies the surgical effect is multifactorial, so reproducing one hormone is unlikely to reproduce the outcome.
Concern: the window may simply be too narrow
The intranasal failure was not a formulation problem so much as a pharmacological one. If satiety and nausea are mediated by overlapping circuitry, no delivery route separates them.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Essentially no community experience
PYY barely appears in research-peptide catalogues, and where it does, reports are minimal. There is no meaningful anecdotal base to document.
Nausea in what reports exist
Consistent with everything the clinical development history predicts.
Very short duration
Reported effects lasting hours at most, which matches a minutes-long half-life administered subcutaneously.
02 Adverse effects & risks
Adverse effects, contraindications and unknowns. The grey-market tier is where under-reporting is worst: uncontrolled use produces no systematic safety surveillance at all, so absence of a reported harm is not evidence of safety.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Nausea and vomiting — dose-limiting [3]
The defining adverse effect and the reason the intranasal programme stopped. Not a tolerability nuisance but the factor that determines whether the compound is usable at all.
No long-term human safety data
Development has not progressed far enough to generate chronic exposure data for any PYY analogue.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Compounded nausea with GLP-1 agonists
The obvious risk of the combination approach that is currently being developed — two agents whose dose-limiting effect is the same one.
Unknown consequences of chronic Y2 agonism
Y2 receptors are expressed beyond the hypothalamus, including in the gut and cardiovascular system. Sustained agonism has no characterisation.
Product identity is essentially unverifiable
With no standardised consumer formulation and an unstable peptide, anything sold under this name is difficult to assess.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Nausea
The only consistently reported effect.
03 Dosing ranges
Figures below are documented, not recommended. Study ranges come from published protocols in the stated model; grey-market ranges are what the research community reports using and carry no safety validation of any kind.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Infusion dosing in human studies [1]
The foundational human work used intravenous infusion at doses producing physiological postprandial concentrations. Neither the route nor the schedule maps onto anything obtainable outside a research setting.
No established therapeutic dose
No PYY analogue has reached approval, so no dose has been established for any route.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
The dose ceiling is nausea, not efficacy
Unusually, the constraint on this compound is not how much is needed but how much is tolerated — and the two overlap.
Combination at sub-nausea doses is the current strategy
Development has moved to pairing lower PYY doses with a GLP-1 agonist rather than pushing PYY alone. That is where any future evidence will come from.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
No meaningful community dosing exists
Too rare, too unstable, and too unpleasant at effective doses to have developed a practice.
04 Synergy & interactions
Combination effects. Almost no peptide combination has been studied as a combination in humans; stack logic is overwhelmingly mechanistic inference and community practice. Each linked compound has its own page.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
PYY plus GLP-1 — the active development direction [4]
Combination programmes pairing Y2-selective analogues with GLP-1 receptor agonists are where the clinical work now sits, on the basis that both are L-cell hormones acting through complementary circuitry.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
Additive satiety, additive nausea
Both halves of the combination follow from the same overlapping circuitry. The strategy is to find doses where the first outruns the second.
Conceptually parallel to amylin plus incretin
The same architecture as CagriSema — a second satiety pathway added to an incretin backbone. Amylin has got considerably further.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Not present in community stacks
Availability rather than reasoning is the limiting factor.
05 Protocols
Whole schedules — dosing, titration, cycle length, and off-time — as documented in trials, as proposed from mechanism, and as circulated in the research community. Reproduced for study and comparison only.
Highest confidenceReported in peer-reviewed literature, registered clinical trials, or regulatory filings. Note the model: much peptide literature is in vitro or rodent work, not human trial data.
Infusion study design [1]
Controlled infusion to physiological postprandial concentrations, with subsequent ad libitum meal intake as the endpoint.
Unproven — inference onlyExtrapolated from a known mechanism, receptor profile, or adjacent compound class. Biologically plausible but not directly demonstrated for this compound in this context.
There is nothing to construct a protocol from
No dose, no route, no formulation, no safety data. This is a target to watch rather than a compound to use.
Uncontrolled reportsAggregated from research-community logs, forums, vendor literature and self-reported experience. Uncontrolled, unverified, subject to placebo, polypharmacy and product-purity confounds. Lowest evidentiary weight.
Not part of any documented protocol
Neither documented protocol includes it, and no community protocol has developed.
05b Condition-specific interest
PYY is one of the hormones that explains why bariatric surgery works, which makes it one of the more genuinely interesting satiety signals in human physiology. It is also a compound whose clinical programme failed for a specific and instructive reason.
No approval, no trial
No PYY analogue is approved anywhere, and no consumer formulation exists. The intranasal development programme was abandoned because the dose producing satiety could not be separated from the dose producing nausea. Anything sold as PYY has no established route, dose or human efficacy data.
Study — human physiology, well established
Bariatric surgery — what PYY explains
Pathophysiology
Roux-en-Y gastric bypass and sleeve gastrectomy produce weight loss and diabetes remission far beyond what restriction alone accounts for, and the metabolic improvement frequently precedes meaningful weight loss.
Mechanistic rationale
PYY and GLP-1 both rise substantially after these operations, and that hormonal change is a large part of why surgery outperforms every non-surgical approach. Blocking those signals attenuates the effect. This is the strongest evidence that PYY does something real in humans — it just was not generated by giving anyone PYY.
Community reports
Not a community topic. It is the reason the compound was pursued at all.
Components carrying the argument: Y2 receptor — hindbrain and hypothalamic satiety
Study — and the failure is the finding
Obesity — the programme that failed
Pathophysiology
PYY 3-36 signals meal termination through Y2 receptors, reducing subsequent intake in controlled human feeding studies.
Mechanistic rationale
The acute effect on food intake is real and reproducible in a laboratory setting. The intranasal development programme could not find a therapeutic window: doses producing meaningful satiety produced nausea, and doses avoiding nausea did not produce useful satiety. That is a pharmacological dead end rather than a funding failure, and it is why no product exists two decades later.
Community reports
Sold in the grey market on the satiety literature, without the part where the window could not be found.
Components carrying the argument: Y2 receptor agonism
Theorized — where the field actually went
The combination approach
Pathophysiology
Appetite is regulated by multiple redundant signals, which is why single-hormone approaches tend to be overwhelmed by compensation.
Mechanistic rationale
Combining PYY with GLP-1 has been studied on the reasoning that lower doses of each might give additive satiety with less nausea from either — which is a sensible response to the window problem. The field has largely moved to unimolecular multi-agonists instead — tirzepatide, retatrutide, CagriSema — which achieve combination pharmacology in a single characterised molecule with defined ratios.
Community reports
Community stacking of PYY with an incretin mirrors the studied idea without the dose-finding.
Components carrying the argument: Y2 plus GLP-1 receptor
Actionable
What to take from this page
Pathophysiology
Not a condition.
Mechanistic rationale
A hormone with a genuine, demonstrated role in human physiology can still be undruggable, and PYY is the cleanest example of that in this library. The gap between "this molecule matters" and "administering this molecule helps" is where most of the compounds on this site live, and here the gap was measured and found to be unbridgeable by that route.
Community reports
—
Components carrying the argument: —
| Question | Position |
|---|---|
| Approved anywhere? | No — no analogue, no product |
| Does PYY do something real? | Yes — it partly explains bariatric surgery |
| Why did development fail? | No window between satiety and nausea |
| Where the field went | Unimolecular multi-agonists with defined ratios |
| Consumer formulation | None exists — no route, no dose |
What actually has evidence for these conditions
For obesity: the incretin class now has the largest pharmacological effect with cardiovascular outcome data behind it. Bariatric surgery still produces the largest and most durable results of any intervention and remains under-referred — and PYY is part of the explanation for why. Resistance training preserves lean mass during weight loss, protein and sleep both matter, and treating undiagnosed obstructive sleep apnoea changes more than people expect.
06 Handling, reconstitution & storage
Physical-chemistry reference for laboratory handling of the lyophilised material. Reproduced so that stability and concentration mathematics can be studied — see the calculator for the arithmetic and the reconstitution guide for sterile technique.
Reconstitution
Where supplied at all, PYY3-36 comes lyophilised in small quantities. It is an unstable peptide with a minutes-long half-life, and no consumer delivery route has been validated.
Storage
Lyophilised: −20 °C. Reconstituted: refrigerated and used promptly — stability in solution is poor.
Common vial sizes
Rarely stocked; where present, typically small milligram quantities.
Stability notes
Chemical instability is one of the principal reasons no consumer-grade formulation exists. This is a genuine limitation rather than a handling inconvenience.
07 Legal & regulatory status
Regulatory status changes and differs by country. This is a summary for orientation, not legal advice — check your own jurisdiction.
Not approved anywhere. No PYY analogue has reached approval for any indication. The intranasal PYY3-36 programme was discontinued on tolerability grounds, and current development is focused on long-acting Y2-selective analogues as combination partners rather than as standalone agents.
PYY is largely absent from consumer grey-market channels for practical chemistry reasons — instability, a very short half-life, and no validated delivery route.
Regulatory and trial claims re-checked against primary sources on 16 August 2026. Checked: no approved analogue; no consumer formulation. Approvals, trial readouts and compounding decisions move faster than anything else on this page — a date here means someone looked, not that nothing has changed since.
Anti-doping
Athletes subject to WADA, USADA, UKAD, NCAA or military testing should assume any peptide is prohibited unless they have verified otherwise against the current WADA Prohibited List. Several classes here (growth-hormone secretagogues, TB-4 analogues, metabolic modulators) are explicitly named. Check the current list — it is republished annually.
§ Sources & further reading
Links resolve to PubMed records, trial registries, publisher pages or primary documents. Where a body of work rather than a single paper is cited, the link opens a PubMed query so the full result set — including newer papers than this page — can be reviewed. Verify every claim against the primary source before relying on it.
- Batterham RL, et al. Gut hormone PYY3-36 physiologically inhibits food intake. Nature. 2002;418(6898):650–654.Human clinical study
- PubMed: PYY and GLP-1 after bariatric surgery — hormonal contribution to appetite change (live query)Database or literature search
- PubMed: intranasal PYY3-36 — tolerability and development history (live query)Database or literature search
- ClinicalTrials.gov: registered PYY analogue trials, including GLP-1 combination programmesRegistered clinical trial
Reminder
For educational and research reference only. Nothing on this site is medical advice, a recommendation, or an instruction to administer any substance to a human being. Every figure on this page is a record of what has been reported, not a recommendation. Full disclaimer.