LY3457263 for Type 2 Diabetes

Recruiting at 39 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must be taking: Semaglutide, Tirzepatide

Must not be taking: Insulin, DPP-4i

Disqualifiers: Type 1 diabetes, Obesity surgery, Cardiovascular conditions, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 months

240 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effects of a new treatment, LY3457263, to determine its potential in lowering blood sugar levels in individuals with Type 2 diabetes. Researchers aim to compare different doses of LY3457263 against a placebo to assess its effectiveness in controlling hemoglobin A1c, a key measure of blood sugar control. Participants should have Type 2 diabetes, a body mass index (BMI) of 27 or higher, and be on a stable dose of semaglutide or tirzepatide, yet still struggle to control their blood sugar levels. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are on a stable dose of semaglutide or tirzepatide, you can continue taking it. If you are taking other oral diabetes medications, you may need to stop them at least 3 months before joining the trial, unless they are metformin, SGLT2 inhibitors, alpha-glucosidase inhibitors, sulfonylureas, or TZDs, which you can continue if the dose has been stable for at least 3 months.

Is there any evidence suggesting that LY3457263 is likely to be safe for humans?

Research has shown that LY3457263 has been tested in both healthy individuals and those with type 2 diabetes. These studies have assessed its safety and tolerability. Results indicate that its safety profile is similar to other drugs in the same category, known as incretin-based treatments, suggesting that LY3457263 is generally well-tolerated with manageable side effects.

One study suggested that LY3457263 works by mimicking a natural hormone that helps control appetite, which can be beneficial for treating conditions like obesity and diabetes. While these studies provide a general expectation, individual experiences may vary.

The trial is currently in Phase 2, focusing on determining the right dose and further evaluating safety. This phase indicates that the treatment has already demonstrated some safety in earlier studies. Overall, LY3457263 appears well-tolerated, but anyone considering joining the trial should discuss it with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for type 2 diabetes?

Researchers are excited about LY3457263 for Type 2 Diabetes because it offers a novel approach to managing blood sugar levels. Unlike traditional treatments that often focus on insulin or metformin to enhance insulin sensitivity or secretion, LY3457263 is being explored for its unique mechanism of action, which may provide a new pathway for glucose regulation. This treatment is administered subcutaneously, which could offer different dosing flexibility and potentially improve patient adherence compared to some oral medications. By introducing a fresh mechanism and delivery method, LY3457263 holds promise for enhancing diabetes management and improving quality of life for patients.

What evidence suggests that LY3457263 might be an effective treatment for type 2 diabetes?

Research has shown that LY3457263 may help lower HbA1c levels, key indicators of blood sugar, in people with type 2 diabetes. One study found that a single dose of LY3457263 was safe, with effects lasting up to 43 days, suggesting it might help stabilize blood sugar levels. This trial will test different doses of LY3457263 to further evaluate its effectiveness and safety. Although more information is needed, these early results offer promise for those not achieving their blood sugar goals with current treatments. ^{2 5 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with type 2 diabetes who are overweight (BMI ≥27 kg/m2) and have not reached their HbA1c goal despite being on a stable dose of semaglutide or tirzepatide. They should have maintained a stable weight and treatment for at least three months. Excluded are those using insulin, other diabetes medications recently, or having certain cardiovascular conditions.

Inclusion Criteria

Were you diagnosed with Type 2 Diabetes before Jan 2025?

Have your diabetes medicines stayed the same for the past 3 months?

Do you use insulin injections or weekly drugs like Ozempic, Wegovy, Mounjaro, or Trulicity?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3457263 or placebo subcutaneously once weekly

8 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3457263

Trial Overview

The study tests LY3457263 against a placebo in participants with type 2 diabetes already taking semaglutide or tirzepatide but still above target blood sugar levels. The main focus is to see if this new drug can better control HbA1c over about nine months.

How Is the Trial Designed?

Group I: LY3457263 Dose 3 Experimental Treatment 1 Intervention

Participants will receive LY3457263 SC

Group II: LY3457263 Dose 2 Experimental Treatment 1 Intervention

Participants will receive LY3457263 SC

Group III: LY3457263 Dose 1 Experimental Treatment 1 Intervention

Participants will receive LY3457263 subcutaneously (SC)

Group IV: Placebo Placebo Group 1 Intervention

Participants will receive placebo SC

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

JY09, a long-acting GLP-1 receptor agonist, demonstrated a dose-dependent increase in drug levels and was well tolerated in healthy subjects, with a half-life of approximately 9.3 days.

The drug effectively increased C-peptide levels after an oral glucose tolerance test at the highest dose, indicating its potential efficacy in enhancing insulin secretion without causing symptomatic hypoglycemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, and tolerability of JY09 in healthy Chinese subjects: A titrating, dose-escalating study. Yang, G., Cao, B., Yang, Y., et al.[2020]

In a phase 2 study involving 316 participants with poorly controlled type 2 diabetes, the dual receptor agonist LY3298176 demonstrated significantly better glucose control and weight loss compared to dulaglutide, with a dose-dependent reduction in HbA1c levels.

LY3298176 was generally well-tolerated, with gastrointestinal side effects being the most common but mostly mild to moderate, indicating a favorable safety profile for this new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Frias, JP., Nauck, MA., Van, J., et al.[2022]

LY3437943 is a novel triple agonist that targets three receptors related to metabolism, showing promising results in obese mice by reducing body weight and improving blood sugar control.

In a phase 1 study, LY3437943 demonstrated a safety profile similar to existing treatments and supported once-weekly dosing, with weight loss effects lasting up to 43 days after a single dose.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple glucagon, GIP, and GLP-1 receptor agonist for glycemic control and weight loss: From discovery to clinical proof of concept. Coskun, T., Urva, S., Roell, WC., et al.[2022]

In a 12-week study involving 72 adults with type 2 diabetes, the multi-receptor agonist LY3437943 demonstrated a good safety profile, with gastrointestinal disorders being the most common side effects.

LY3437943 significantly reduced daily plasma glucose and HbA1c levels, as well as body weight, in a dose-dependent manner, supporting its potential for once-weekly dosing and further development in treating type 2 diabetes and obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Urva, S., Coskun, T., Loh, MT., et al.[2022]

Citations

1.

withpower.com

withpower.com/trial/phase-2-diabetes-mellitus-3-2025-b7feb

LY3457263 for Type 2 Diabetes

In a study, it was given once a week and was found to be safe, with effects lasting up to 43 days after a single dose.

2.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06897475

NCT06897475 | A Study of LY3457263 Compared With ...

The purpose of this study is to measure the change in hemoglobin A1c (HbA1c) with LY3457263 compared with placebo in participants with type 2 diabetes who ...

3.

trials.lilly.com

trials.lilly.com/en-US/trial/587456

A Study of LY3457263 Compared With Placebo in Participants ...

The purpose of this study is to measure the change in hemoglobin A1c (HbA1c) with LY3457263 compared to placebo in participants with type 2 diabetes.

4.

trial.medpath.com

trial.medpath.com/clinical-trial/d5f74243f74e515b/ly3457263-type2-diabetes-semaglutide-tirzepatide

A Study of LY3457263 Compared With Placebo in Participants ...

The purpose of this study is to measure the change in hemoglobin A1c (HbA1c) with LY3457263 compared with placebo in participants with type 2 diabetes who ...

5.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/40214900/

Efficacy and Safety of Tirzepatide Compared with GLP-1 ...

Tirzepatide demonstrated statistically significantly greater reductions in HbA1c and body weight when compared with selected GLP-1 RAs and ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04641312

A Study of LY3457263 in Healthy Participants and ...

The main purpose of this study is to investigate the safety and tolerability of the study drug LY3457263 in healthy participants and participants with type 2 ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05377333

NCT05377333 | A Study of LY3457263 Alone and in ...

The main purpose of this study is to investigate the safety and tolerability of the study drug LY3457263 when administered alone or in combination with glucagon ...

8.

medchemexpress.com

medchemexpress.com/nisotirostide.html?srsltid=AfmBOorWI6NpteDpgMVgozDUohCJDxTQSvL0vDl7Z2tYeq5MiGqLoKGp

Nisotirostide (LY-3457263) | NPY2R Agonist

By mimicking peptide YY (PYY), Nisotirotide inhibits appetite and can be used in the research of diseases such as obesity and diabetes. Clinical Trial. NCT ...