What is Nisotirostide?

Nisotirostide is an investigational once-weekly injectable peptide from Eli Lilly that selectively activates the neuropeptide Y2 receptor, mimicking the gut satiety hormone peptide YY. It is not approved by any regulator and has completed only a Phase 1 study, reported October 3, 2026 in Molecular Metabolism as adjunctive therapy to GLP-1 receptor agonists for type 2 diabetes and obesity.

Is Nisotirostide approved for medical use?

Nisotirostide is investigational: it is being studied in clinical research and is not an approved medicine. United States (FDA): Not approved; investigational. Only a completed Phase 1 study has been reported as of October 2026, with no New Drug Application filed. European Union (EMA): Not authorised; investigational, no marketing authorization. Australia (TGA): Not entered on the ARTG; investigational only and not approved for supply.

Is Nisotirostide legal in Australia?

Nisotirostide in Australia (TGA): Not entered on the ARTG; investigational only and not approved for supply.

Is Nisotirostide banned in sport?

Nisotirostide under the World Anti-Doping Agency (WADA) code: Not listed on the WADA Prohibited List. As an investigational agent with no approved therapeutic use, it would fall under the S0 (non-approved substances) category, which is prohibited at all times.

Selective neuropeptide Y2 receptor (NPY2R) agonist (investigational, peptide YY-mimetic)

Nisotirostide

Investigationalaka LY3457263, LY-3457263

Nisotirostide is being developed as an add-on to GLP-1 receptor agonist therapy rather than as a standalone treatment. A Molecular Metabolism paper published October 3, 2026 reported preclinical mouse data and a completed Phase 1 single ascending dose study (NCT04641312, n=65) in healthy participants and people with type 2 diabetes already taking dulaglutide. It remains in early clinical development and is not authorized for any medical use.

Mechanism

In plain terms, nisotirostide copies a natural gut hormone, peptide YY, that signals fullness after eating. Technically, it is a selective agonist of the neuropeptide Y2 receptor (NPY2R). In mouse models it reduced body weight by up to 12% as monotherapy and up to 31% when combined with a GLP-1 receptor agonist, an effect the study authors described as synergistic, with glucose-control benefits reported to be independent of weight loss.

Regulatory Status by Region

United States (FDA)Not approved; investigational. Only a completed Phase 1 study has been reported as of October 2026, with no New Drug Application filed.
Australia (TGA)Not entered on the ARTG; investigational only and not approved for supply.
European Union (EMA)Not authorised; investigational, no marketing authorization.
WADANot listed on the WADA Prohibited List. As an investigational agent with no approved therapeutic use, it would fall under the S0 (non-approved substances) category, which is prohibited at all times.

See the full regulatory status matrix

Key Studies

Nisotirostide (LY3457263), a novel NPY2 receptor agonist for type 2 diabetes and obesity: From discovery to clinical proof of concept (opens in a new tab) (Briere DA, et al. Mol Metab. 2026 Oct 3:102452; DOI 10.1016/j.molmet.2026.102452; PMID 42829171)
A Study of LY3457263 in Healthy Participants and Participants With Type 2 Diabetes (Phase 1, with dulaglutide) (opens in a new tab) (ClinicalTrials.gov NCT04641312; sponsor Eli Lilly and Company; completed)

Related Clinical Trials

Eli Lilly Discloses Phase 1 Data on Nisotirostide, a Novel NPY2 Receptor Agonist Designed to Add to GLP-1 TherapyResearch · Oct 4, 2026

Latest research

Nisotirostide (LY3457263), a novel NPY2 receptor agonist for type 2 diabetes and obesity: From discovery to clinical proof of concept. (opens in a new tab)
Molecular metabolism · Oct 3, 2026

See all recent Nisotirostide research

Common Questions

What is Nisotirostide?: Nisotirostide is an investigational once-weekly injectable peptide from Eli Lilly that selectively activates the neuropeptide Y2 receptor, mimicking the gut satiety hormone peptide YY. It is not approved by any regulator and has completed only a Phase 1 study, reported October 3, 2026 in Molecular Metabolism as adjunctive therapy to GLP-1 receptor agonists for type 2 diabetes and obesity.
Is Nisotirostide approved for medical use?: Nisotirostide is investigational: it is being studied in clinical research and is not an approved medicine. United States (FDA): Not approved; investigational. Only a completed Phase 1 study has been reported as of October 2026, with no New Drug Application filed. European Union (EMA): Not authorised; investigational, no marketing authorization. Australia (TGA): Not entered on the ARTG; investigational only and not approved for supply.
How does Nisotirostide work?: In plain terms, nisotirostide copies a natural gut hormone, peptide YY, that signals fullness after eating. Technically, it is a selective agonist of the neuropeptide Y2 receptor (NPY2R).
Is Nisotirostide legal in Australia?: Nisotirostide in Australia (TGA): Not entered on the ARTG; investigational only and not approved for supply.
Is Nisotirostide banned in sport?: Nisotirostide under the World Anti-Doping Agency (WADA) code: Not listed on the WADA Prohibited List. As an investigational agent with no approved therapeutic use, it would fall under the S0 (non-approved substances) category, which is prohibited at all times.