LY3457263 for Type 2 Diabetes

Recruiting at 55 trial locations

Overseen By There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

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

Trial Summary

What is the purpose of this trial?

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 are not at HbA1c goal when treated with a stable dose of semaglutide or tirzepatide. Participation in the study will last about 9 months.

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.

What safety data exists for LY3457263 in humans?

LY3437943, which may be similar to LY3457263, was tested in people with type 2 diabetes and showed a safety profile similar to other incretin-based treatments, which are generally well-tolerated. 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. ^{1 2 3 4 5}

What makes the drug LY3457263 unique for treating type 2 diabetes?

LY3457263 is unique because it is a multi-receptor agonist that targets three different receptors: glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1). This approach can help improve blood sugar control and support weight loss, offering a novel way to manage type 2 diabetes compared to treatments that target only one receptor. ^{1 2 3 4 6}

Research Team

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Eligibility Criteria

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

Have a body mass index (BMI) of ≥27 kg/m2 at screening

Have had a stable body weight for the three months prior to screening

I have been on a stable dose of semaglutide or tirzepatide for at least 3 months.

Exclusion Criteria

I have not used weight loss medications or remedies in the last 3 months.

I have used insulin in the last year to manage my blood sugar.

I have had or am planning to have surgery for weight loss.

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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]

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]

References

1. England 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. [2022]

2. United States 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. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Efficacy and Safety of the Glucagon Receptor Antagonist LY2409021 in Patients With Type 2 Diabetes: 12- and 24-Week Phase 2 Studies. [2022]

4. England 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. [2022]

5. Germany pubmed.ncbi.nlm.nih.gov

Pharmacokinetics, pharmacodynamics, and tolerability of JY09 in healthy Chinese subjects: A titrating, dose-escalating study. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Intensive multifactorial treatment modifies the effect of family history of diabetes on glycaemic control in people with Type 2 diabetes: a post hoc analysis of the ADDITION-Denmark randomized controlled trial. [2022]