A Study of LY3457263 in Obese Participants

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 1

Sponsor: Eli Lilly and Company

Disqualifiers: Hypertension, Abnormal ECG, Diabetes

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing a new drug called LY3457263 together with tirzepatide to see if they are safe and well-tolerated in overweight or obese people. The study will also measure how much of LY3457263 gets into the bloodstream and how long it stays in the body. The trial will last a few months.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the study involves evaluating new medications, it's possible that some changes to your current medication regimen might be required. Please consult with the trial coordinators for specific guidance.

How is the drug LY3457263 (Tirzepatide) different from other treatments for type 2 diabetes?

LY3457263 (Tirzepatide) is unique because it is a dual agonist, meaning it activates both GIP and GLP-1 receptors, which can enhance insulin release and improve blood sugar control more effectively than treatments targeting only GLP-1 receptors. ^{1 2 3 4 5}

What data supports the effectiveness of the drug LY3457263?

Research shows that tirzepatide, a component of LY3457263, is effective in lowering blood sugar levels and body weight in people with type 2 diabetes. It works by activating two hormones that help control blood sugar and appetite. ^{6 7 8 9 10}

Who Is on the 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

Are You a Good Fit for This Trial?

Inclusion Criteria

You are male or female.

Participants who are overtly healthy as determined by medical evaluation

Your weight and body mass index (BMI) fall within a specific range of 27.0 to 45.0 kilograms per meter squared (kg/m²).

Exclusion Criteria

Have a mean sitting systolic blood pressure (BP) higher than 160 millimeters of mercury (mmHg) or a mean sitting diastolic BP higher than 90 mmHg from 3 measurements

Have an abnormal 12-lead electrocardiogram (ECG) at screening

Have type 1 or type 2 diabetes mellitus

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive multiple doses of LY3457263 in combination with tirzepatide

6 weeks

Weekly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3457263
• Placebo
• Tirzepatide

How Is the Trial Designed?

Group I: LY3457263 + Tirzepatide Experimental Treatment 2 Interventions

LY3457263 administered subcutaneously (SC) in combination with tirzepatide given SC.

Group II: Placebo + Tirzepatide Placebo Group 2 Interventions

Placebo administered SC in combination with tirzepatide given 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

Tirzepatide, approved in 2022, is a novel treatment for type 2 diabetes that acts on both GLP-1 and GIP pathways, showing significant efficacy in lowering blood sugar levels and promoting weight loss in various patient groups.

Clinical trials, including the SURPASS and SURMOUNT studies, indicate that tirzepatide has a safety profile similar to traditional GLP-1 receptor agonists, with common gastrointestinal side effects, making it a promising option for patients needing better glycemic and weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. Krauss, Z., Hintz, A., Fisk, R.[2023]

Tirzepatide, a medication for type 2 diabetes, shows a dose-dependent increase in gastrointestinal adverse events (AEs), with nausea and diarrhea being the most common, affecting up to 49% of participants at the highest dose (15 mg).

Despite the gastrointestinal side effects, serious adverse events like severe hypoglycemia and acute pancreatitis are rare (≤ 1%), indicating that tirzepatide is generally safe for use in patients with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Events Related to Tirzepatide. Mishra, R., Raj, R., Elshimy, G., et al.[2023]

In a study involving 2002 adults with type 2 diabetes and high cardiovascular risk, tirzepatide significantly reduced HbA1c levels more than insulin glargine after 52 weeks, with reductions of -2.43% and -2.58% for tirzepatide 10 mg and 15 mg, respectively, compared to -1.44% for glargine.

Tirzepatide was associated with a lower incidence of hypoglycemia (6-9%) compared to glargine (19%), and it did not increase cardiovascular risk, showing it is a safe and effective option for managing diabetes in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Del Prato, S., Kahn, SE., Pavo, I., et al.[2022]

LY3298176, a dual GIP and GLP-1 receptor agonist, demonstrated significant improvements in glycemic control and body weight reduction in both preclinical studies and a Phase 1b trial involving 142 subjects with type 2 diabetes mellitus (T2DM).

The most common side effects were mild to moderate gastrointestinal issues, which were dose-dependent, indicating that while LY3298176 is effective, monitoring for these side effects is important during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Coskun, T., Sloop, KW., Loghin, C., et al.[2021]

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]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Tirzepatide: Clinical review of the "twincretin" injectable. [2023]

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

Adverse Events Related to Tirzepatide. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

The importance of glucose-dependent insulinotropic polypeptide receptor activation for the effects of tirzepatide. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. [2022]

6. Germany pubmed.ncbi.nlm.nih.gov

LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. [2021]

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

Genetically Predicted Glucose-Dependent Insulinotropic Polypeptide (GIP) Levels and Cardiovascular Disease Risk Are Driven by Distinct Causal Variants in the GIPR Region. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Enhanced agonist residence time, internalization rate and signalling of the GIP receptor variant [E354Q] facilitate receptor desensitization and long-term impairment of the GIP system. [2021]

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

Localization of glucose-dependent insulinotropic polypeptide (GIP) to a gene cluster on chromosome 17q. [2007]

10. 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]