Nisotirostide (LY3457263)_Dosage, benefits & legal status
Also known as LY3457263, LY-3457263
A gut-hormone analog that only works as an add-on.
Common vial size is what vendors typically sell, not a recommendation. Enter your own vial in the calculator.
What is Nisotirostide (LY3457263)?
Plain language first. The technical label stays, but it never stands alone.Overview
This is the engineered version of a hormone this site already covers. Peptide YY is the gut hormone that suppresses appetite when infused into a vein and did nothing when injected under the skin, and nisotirostide is Lilly's attempt to fix that. The honest summary of the human data is narrow. By itself it took off 0.75 kg more than placebo, and that result was not statistically significant. Added on top of a GLP-1 drug it took off 2.58 kg more than the GLP-1 drug alone, and that was significant. If you have seen 12 percent or 31 percent weight loss attached to this compound, those are mouse numbers from the same paper, not human ones. Nausea and vomiting were the most common side effects and got worse with higher doses.
Nisotirostide is a potent and selective agonist at the NPY2 receptor, engineered from the PYY family and developed as an add-on to GLP-1 receptor agonists for type 2 diabetes and obesity. Its discovery-to-proof-of-concept paper was published in October 2026. In a phase 1 study of 65 participants, comprising healthy volunteers and people with type 2 diabetes on weekly dulaglutide, single subcutaneous doses from 0.025 to 1 mg produced a mean weight reduction of 0.75 kg against placebo as monotherapy, and that was not statistically significant, while addition to dulaglutide produced a 2.58 kg greater reduction than dulaglutide alone, and that was significant. A phase 2 trial of about 200 participants is adding it to established semaglutide or tirzepatide in type 2 diabetes, with HbA1c at week 24 as the primary endpoint.
What it's used for
Nothing. It has no approval anywhere. It is in phase 2 development as an addition to existing GLP-1 treatment in type 2 diabetes.
How does Nisotirostide (LY3457263) work?
What it does in the body, and where.To understand this compound, start from the peptide YY page on this site. Nisotirostide is an attempt to solve the exact problem that page describes.
- 01The problem it was built forPeptide YY, in its PYY(3-36) form, suppresses appetite through the Y2 receptor when it is infused into a vein. Given as an ordinary injection under the skin it has not delivered, because the native peptide is cleared quickly and the dose needed to work brings nausea with it. Engineering a longer-acting, more selective Y2 agonist is the obvious response, and that is what this is.
- 02What selective means hereThe NPY family signals through four functional human receptors, Y1, Y2, Y4 and Y5. Appetite suppression by PYY runs through Y2, while Y1 handles blood vessel constriction and Y5 is tied to feeding stimulation. A compound aimed at Y2 and quiet at the others is trying to isolate the appetite effect from the rest, and the published work reports potent and selective activation of Y2 signaling.
- 03The mouse results, and why they are quoted so oftenIn mice the compound reduced body weight by up to 12 percent alone and up to 31 percent combined with a GLP-1 agonist, and improved glucose control in a way that did not depend on the weight loss. Those are striking numbers and they are the ones that travel. They are also mouse numbers, stated as such in the paper's own abstract.
- 04What happened in peopleSixty-five participants, single doses from 0.025 to 1 mg. As monotherapy at the top dose the weight difference against placebo was 0.75 kg and was not statistically significant. Added to dulaglutide it produced 2.58 kg more weight loss than dulaglutide alone, and that was significant. So the human data supports the add-on strategy and does not support the compound working by itself. The 2.58 kg figure is also the honest headline, not the 31 percent.
- 05Where it sits beside the other NPY2 program on this siteBI 3034701, already covered here, is a triple agonist that swaps glucagon for NPY2 and bundles everything into one molecule. Nisotirostide takes the other approach: isolate NPY2 in its own molecule and add it to whatever GLP-1 drug someone is already taking. The phase 2 design reflects that, enrolling people already stable on semaglutide or tirzepatide.
What else is it used for?
Each group carries its own evidence level.Approved means regulators have cleared it for that purpose. Investigational means it is in trials. Early research means it is being studied and is not established.
The human results, stated plainly
Early research- Human trialMonotherapy in humans: mean weight reduction of 0.75 kg against placebo, not statistically significant.
- Human trialAdded to dulaglutide: 2.58 kg greater reduction than dulaglutide alone, p below 0.05.
- human-earlyThe whole human record is one phase 1 of 65 participants given single subcutaneous doses from 0.025 to 1 mg.
- human-earlyNausea and vomiting were the most common adverse events, dose-dependent and mild to moderate, with no published percentages.
The numbers that are from mice
none- Animal studyUp to 12 percent weight reduction as monotherapy and up to 31 percent combined with a GLP-1 agonist were measured in mice, and the paper's own abstract says so.
- Animal studyMice also showed glucose improvements independent of weight loss.
What the development plan tells you
Investigational- Human trialThe phase 2 enrolls people already stable on semaglutide or tirzepatide and uses HbA1c at week 24 as its primary endpoint, not weight. It is designed as an add-on.
- No dataNo residue count or sequence has been published. A Lilly patent covering 34-residue PYY(3-36) analogs shares three inventors with the paper but never names this compound, so the 34 amino acid description is inference.
The 12 percent and 31 percent weight-loss figures are the problem. They are real numbers from the paper and they were measured in mice, and they are the numbers most likely to reach a reader detached from the species. The human monotherapy result was 0.75 kg against placebo and did not reach statistical significance. The useful human number is 2.58 kg of additional weight loss on top of dulaglutide. Second, this is often described as a 34 amino acid peptide; no source states a residue count for it, and that figure is an inference from a patent that never names the compound. No sequence has been published. Third, the phase 2 is a diabetes trial with HbA1c at week 24 as its primary endpoint, so it is not designed to produce a weight headline. Last, it should not be confused with peptide YY itself, the natural 36-residue hormone, or with BI 3034701, a triple agonist that bundles NPY2 activity into a triple agonist rather than isolating it.
The published record
Papers and trials about Nisotirostide (LY3457263)
Searched: nisotirostide, LY3457263, LY-3457263.
Left out: peptide YY (has its own slug and a large literature; this molecule is engineered from that family and would be swamped by it); PYY (same problem, and it also matches PYY(3-36) which belongs to the peptide YY slug); NPY2 (a receptor term that also pulls BI 3034701 and the neuropeptide Y literature, both with their own slugs); Y2 receptor (same problem); obesity (an enormous clinical literature).
Furthest stage reached: No clinical trial on record
Counted from Europe PMC indexing, not read by a person; a human tag can land on reviews, commentary or lab papers; clinical trial publications is the narrower count.
At a glance
Four things to know about Nisotirostide (LY3457263)
Evidence
Investigational
Category
Weight loss and metabolic
Common vial
Varies
Half-life
Supports once-weekly dosing, no figure published
How much, and do you cycle it?
The range, and whether you take breaks.No established dose, not established. Not applicable No range
No approved product and no established regimen, so no cycling scheme exists.
Supports once-weekly dosing, no figure publishedNo figure
The publication states that its pharmacokinetic profile supports once-weekly dosing but no numeric human half-life is given in the sources read. No figure is plotted rather than quoting one we could not source.
You can compare this against the whole library to see where it sits.
How do I dose and price it?
Enter your vial and your dose. Pick a mix. We show the draw and the cost.The vial holds a fixed amount of drug. Adding more water does not make more drug, it just spreads it thinner, so you draw a bigger number on the syringe for the same dose.
Choose your mix
Measuring the water1 mL = one full 100-unit syringe.
How do you store it?
Before mixing, and after.Nothing to store: it is not sold anywhere.
Nisotirostide (LY3457263) has never been marketed, so there is no vial, pen or bottle to keep at home. Supplies for a trial are made, stored and dispensed by the sponsor and the trial pharmacy under conditions set in the protocol. Anything offered for sale under this name did not come from that supply chain.
What are the side effects and cautions?
Known cautions and warnings for this compound.Who should avoid it
- Any use at all: there is no approved product and no established dose
- Expecting it to work on its own, since the monotherapy result in humans was 0.75 kg and not statistically significant
- Quoting the 12 percent or 31 percent weight-loss figures as human results, because they are from mice
Stop and get help
- Not applicable. There is no approved product.
Common effects
- Nausea and vomiting, dose-dependent and mild to moderate, with no published incidence figures
Where this page says nothing is established, that means nobody has studied it, not that a compound is safe.
Is Nisotirostide (LY3457263) approved?
And where the numbers on this page come from.No. Nisotirostide (LY3457263) is not approved anywhere and is currently in company-run clinical trials. There is no legal route to obtain it outside a trial.
- Approval statusInvestigational
- RouteUnder the skin (subcutaneous)
- Checked30 October 2026
- DoseNo dose has been established in people.
- Vial sizeFrom what vendors typically list; not a recommendation.
- Sources
What has happened recently
Not approved anywhere. The phase 1 study is registered as NCT04641312 and enrolled 65 participants, healthy volunteers plus people with type 2 diabetes on weekly dulaglutide 1.5 mg, using single subcutaneous doses from 0.025 to 1 mg. The phase 2, NCT06897475, is recruiting about 200 participants and adds nisotirostide to stable semaglutide at 1 to 2 mg or tirzepatide at 5 to 15 mg in type 2 diabetes; its primary endpoint is HbA1c at week 24 rather than weight, worth noting for anyone expecting a weight headline from it. Note also what is not established: no source we read states a residue count for this molecule, and no sequence has been published. A granted Lilly patent covers 34-residue PYY(3-36) analogs acylated at an engineered lysine, and three of its inventors are authors of the nisotirostide paper, but the patent never names the compound. So the widely repeated description of it as a 34 amino acid peptide is a reasonable inference rather than a sourced fact, and no sequence appears on this page.
You can compare this against the whole library, or read how to check a seller.
What else is like Nisotirostide (LY3457263)?
Others in Fat loss without GLP-1, side by side.If you're weighing Nisotirostide (LY3457263), it's worth reading Peptide YY, PYY1875 (NNC0165-1875), and Spexin in the same class.
A gut-hormone analog that only works as an add-on.
- Dose
- No established dose
- How often
- Not established
A hormone whose effect survives replication in people and keeps failing to become a medicine.
- Dose
- No established dose
- How often
- Not applicable
A long-acting copy of the gut fullness hormone PYY that Novo Nordisk tested on top of semaglutide. It added 2.15 points of weight loss with frequent nausea, and development ended in 2023.
- Dose
- 1.0 mg once weekly, added to semaglutide 2.4 mg (phase 2 trial)
- How often
- Once weekly (phase 2 trial)
An appetite peptide found by computer search, still almost entirely in animals.
- Dose
- Research only
- How often
- Not established
Guides for this compound
- How to Reconstitute a Peptide
Mix peptide powder with bacteriostatic water, step by step.
- How to Read an Insulin Syringe
Read the units, convert to millilitres, and draw the exact dose.
- mcg vs mg: The Peptide Dosing Mistake to Avoid
Your vial says mg and your protocol says mcg. Here is the conversion and how to check it.
- How to Read a Peptide COA
What the purity number does and does not tell you, and how to spot an edited report.
- How to Vet a Peptide Vendor
Independent COAs, HPLC purity, and the red flags that mean walk away.
Sources
- Briere and colleagues, Molecular Metabolism, discovery to clinical proof of concept(2026)Nisotirostide (LY3457263), a novel NPY2 receptor agonist for type 2 diabetes and obesity: From discovery to clinical proof of concept, volume 114, article 102452, published online October 3, 2026, all authors at Eli Lilly. Reports potent and selective activation of NPY2 receptor signaling in vitro. In mice, body weight reduction of up to 12 percent as monotherapy and up to 31 percent combined with a GLP-1 receptor agonist, with glucose improvements independent of weight loss. In a phase 1 study of 65 participants, healthy volunteers plus people with type 2 diabetes on dulaglutide 1.5 mg weekly, single subcutaneous doses of 0.025 to 1 mg: monotherapy produced a non-significant mean weight reduction of 0.75 kg against placebo, and addition to dulaglutide produced a 2.58 kg greater reduction than dulaglutide alone with p below 0.05. Most common adverse events were gastrointestinal, including nausea and vomiting, dose-dependent and mild to moderate. Trial registration NCT04641312. DOI resolved at Crossref; the 3 October 2026 date is the online publication date, with the print issue dated later.
- Trial registry record NCT06897475, the phase 2(2026)Phase 2, recruiting, about 200 participants planned, adding nisotirostide to stable semaglutide at 1 to 2 mg or tirzepatide at 5 to 15 mg in adults with type 2 diabetes. The primary endpoint is HbA1c at week 24, not body weight. The design is the clearest statement of the development strategy: this is being built as an addition to an existing GLP-1 drug rather than as a standalone treatment.
Beyond these, 1 records are indexed. Browse the records