Nisotirostide

Table of contents

• What is nisotirostide?
• How does nisotirostide work?
• Which conditions is nisotirostide studied for?
• How is nisotirostide given?
• What do the clinical trials show?
• What side effects are known?

What is nisotirostide?

Nisotirostide (development code LY3457263) is an investigational substance being developed by Eli Lilly and Company for the treatment of type 2 diabetes mellitus.^[3] It is a protein-based substance, specifically a new molecular entity, and is classified as an antihyperglycaemic agent — a medicine intended to lower blood sugar levels.^[2] Nisotirostide does not yet have a marketing authorisation in the product records, meaning it is still being studied and is not available as a prescribed medicine.^[1]

How does nisotirostide work?

Nisotirostide acts as a neuropeptide Y receptor agonist, meaning it binds to and activates specific receptors in the body called neuropeptide Y receptors.^[2] These receptors are involved in regulating appetite, energy balance, and glucose metabolism. By activating them, nisotirostide is thought to help lower blood sugar levels in people with type 2 diabetes. The exact way it produces this effect is still being investigated in clinical studies.

Which conditions is nisotirostide studied for?

• Type 2 diabetes mellitus — the main condition being studied. The current Phase 2 trial tests whether adding nisotirostide to existing treatment with semaglutide or tirzepatide can further lower HbA1c in people who have not reached their blood sugar goal.^[1]
• Obesity — nisotirostide was previously investigated for obesity, but no recent development has been reported in this area.^[2]

How is nisotirostide given?

Nisotirostide is given as a solution for injection by subcutaneous use, meaning it is injected under the skin.^[1] In the current trial, it is administered once weekly.^[3]

What do the clinical trials show?

One Phase 2 trial of nisotirostide is currently authorised in the EU Clinical Trials Information System.^[1] The trial is a parallel-group, double-blind study, meaning participants are randomly assigned to receive either nisotirostide or a placebo, and neither the participants nor the researchers know who is receiving which treatment.^[3]

The trial plans to enrol 200 adults aged 18 to 75 years with type 2 diabetes who have been on a stable dose of either semaglutide or tirzepatide for at least three months and have not achieved their HbA1c goal.^[3] HbA1c is a blood test that measures a person's average blood sugar level over the past two to three months.

The main measurement in this trial is the change from baseline in HbA1c at Week 24.^[1] The study aims to learn whether nisotirostide, in combination with semaglutide or tirzepatide, can further reduce HbA1c levels compared to placebo.^[3]

What side effects are known?

The available sources do not provide specific information on side effects of nisotirostide. As an investigational substance, its safety profile is still being established through clinical trials.