LY3457263 + Tirzepatide for Obesity

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and tolerability of a new treatment called LY3457263, administered with tirzepatide (a medication used to help manage weight), for individuals who are overweight or obese. The researchers aim to understand how the body absorbs and processes LY3457263. Some participants will receive the new treatment, while others will receive a placebo (a substance with no active drug) alongside tirzepatide. Suitable candidates for this trial include those with a stable weight and a body mass index (BMI) between 27 and 45, who do not have diabetes and have normal blood pressure. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LY3457263 remains under evaluation for safety. Limited information exists on its effects in humans, making it crucial to monitor new studies for further insights.

Tirzepatide is already used to treat type 2 diabetes and obesity, with common side effects including constipation and stomach pain. While there is a warning about thyroid tumors observed in rats, this has not been proven in humans.

Overall, tirzepatide has been used by many, providing more information compared to LY3457263. However, both treatments continue to be studied together to better understand their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LY3457263 because it offers a fresh approach to tackling obesity by potentially combining two powerful agents. Unlike standard treatments like lifestyle changes, medications such as orlistat, and GLP-1 receptor agonists, LY3457263 is administered alongside tirzepatide, a dual-action drug that targets both the GIP and GLP-1 receptors. This combination could enhance weight loss by improving insulin sensitivity and increasing satiety, making it a promising option for those struggling with obesity. By pairing LY3457263 with tirzepatide, researchers hope to achieve more significant results than current therapies.

What evidence suggests that this trial's treatments could be effective for overweight or obese participants?

Research has shown that tirzepatide aids in weight loss. One study found that 81.6% to 86.4% of participants taking tirzepatide lost at least 5% of their body weight, suggesting it as a promising option for those who are overweight or obese. Tirzepatide also significantly reduced blood sugar levels in individuals with type 2 diabetes. In this trial, one treatment arm combines LY3457263 with tirzepatide to potentially enhance these effects. Although information on LY3457263 remains limited, the combination is still under study, and the success of tirzepatide offers hope for its potential benefits. ^{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

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]

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]

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]

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]

Citations

1. 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 ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/eli-lilly-obesity-therapy/

Eli Lilly's obesity therapy meets co-primary objectives Furthermore, 81.6% and 86.4% of the subjects who received tirzepatide achieved a minimum of 5% body weight loss, the other co-primary endpoint ...

3. trials.lilly.com trials.lilly.com/en-US/find

Find Lilly Clinical Trials A Study to Investigate Effectiveness of Tirzepatide Following Initiation of Ixekizumab in Participants With Active Psoriatic Arthritis and Ove... Enrolling.

4. withpower.com withpower.com/trial/phase-1-obesity-10-2022-59277

A Study of LY3457263 in Obese Participants In a study involving 2002 adults with type 2 diabetes and high cardiovascular risk, tirzepatide significantly reduced HbA1c levels more than insulin glargine ...

5. investor.lilly.com investor.lilly.com/news-releases/news-release-details/lillys-mounjaro-tirzepatide-gipglp-1-dual-agonist-demonstrated

Lilly's Mounjaro (tirzepatide), a GIP/GLP-1 dual agonist ... In the trial, the risk of cardiovascular death, heart attack, or stroke was 8% lower for Mounjaro vs. Trulicity (hazard ratio: 0.92; 95.3% CI: ...

6. 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 ...

7. file.medchemexpress.com file.medchemexpress.com/batch_PDF/HY-P10026/Nisotirostide-SDS-MedChemExpress.pdf

Safety Data Sheet Ensure adequate ventilation. Provide accessible safety shower and eye wash station. Personal protective equipment. Eye protection. Safety ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05582096

NCT05582096 | A Study of LY3457263 in Obese Participants The main purpose of this study is to evaluate the safety and tolerability of LY3457263 when administered in combination with tirzepatitide in overweight or ...

9. medchemexpress.com medchemexpress.com/nisotirostide.html?srsltid=AfmBOoq9jG5YlBwSSEYMOvJPhMuHQl0cztmoB7AkfvhzXwicBSrywUXR

Nisotirostide (LY-3457263) | NPY2R Agonist Nisotirotide (LY-3457263) is a subcutaneous injectable NPY2 receptor agonist. By mimicking peptide YY (PYY), Nisotirotide inhibits appetite and can be used in ...

10. adisinsight.springer.com adisinsight.springer.com/drugs/800061301

Nisotirostide - Eli Lilly and Company - AdisInsight - Springer Nisotirostide (also known as LY 3457263) is a subcutaneously administered therapeutic, being developed by Eli Lilly and Company, ...