LY3841136 + Tirzepatide for Obesity with Type 2 Diabetes

Not currently recruiting at 57 trial locations

Overseen By Jeffrey A Norton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must be taking: Metformin, SGLT2 inhibitors

Disqualifiers: Severe hypoglycemia, Cardiovascular conditions, Renal impairment, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 64 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug LY3841136, alone or combined with Tirzepatide (a medication for weight management), can aid long-term weight management in individuals with Type 2 Diabetes. Researchers aim to assess the safety and effectiveness of these treatments across various doses. The trial spans approximately 64 weeks and seeks participants with Type 2 Diabetes who have faced weight issues for at least three months and manage their diabetes with diet, exercise, or specific medications. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group, providing participants an opportunity to contribute to early findings.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, it requires that any medications you are taking be at a stable dose for at least 3 months before screening.

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

Research has shown that Tirzepatide is generally well-tolerated. The FDA approved it for treating type 2 diabetes in May 2022. Safety data from several studies indicate it is safe, with some people experiencing mild side effects.

Earlier studies on LY3841136 have focused on its use for weight management. Although detailed safety data is limited, its testing with Tirzepatide in a Phase 2 trial suggests promise in earlier research.

Ongoing studies are examining the combination of LY3841136 and Tirzepatide to assess tolerance. While specific safety data for this combination is not detailed, the progression to this trial phase suggests earlier findings were positive enough to continue. Participants may experience some side effects, but these are typically mild, as seen in related treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about LY3841136 and Tirzepatide for treating obesity in people with Type 2 Diabetes because they promise a fresh approach to managing these conditions. Unlike traditional treatments that often focus on either blood sugar control or weight loss separately, this combination targets both issues simultaneously. LY3841136 is a new active ingredient that, when paired with Tirzepatide, a known GLP-1 receptor agonist, could enhance weight loss and improve metabolic health more effectively. This dual-action strategy has the potential to provide better outcomes than current standard medications, which usually address these problems individually.

What evidence suggests that this trial's treatments could be effective for obesity with Type 2 Diabetes?

Research has shown that LY3841136, also known as eloralintide, yields promising results for weight loss in people with obesity. In earlier studies, participants lost between 9% and 20% of their body weight over 48 weeks. In this trial, some participants will receive LY3841136 alone, while others will receive it combined with tirzepatide. Past trials have demonstrated tirzepatide's effectiveness by targeting specific receptors in the body, leading to significant weight loss. When used together in this trial, these treatments might help people with Type 2 Diabetes manage their weight even more effectively. ^{1 3 5 6 7}

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?

This trial is for adults with obesity or overweight who also have Type 2 Diabetes. Participants will be involved in the study for about 64 weeks to test weight management treatments.

Inclusion Criteria

W8M-MC-LAA2: Have a Body Mass Index (BMI) of ≥27 kilograms per square meter (kg/m²)

W8M-MC-LAA2: Have Type 2 Diabetes

W8M-MC-LAA2: Have a HbA1c ≥7.0 % (53 millimoles/mole (mmol/mol)) to ≤10.5% (91 mmol/mol) and treated with diet and exercise alone or with a stable dose of metformin (and not more than the locally approved dose) with or without a sodium-glucose cotransporter 2 (SGLT2) inhibitor for at least 3 months prior to screening

Exclusion Criteria

I have a history of pancreatitis.

W8M-MC-LAA2: Have fasting triglycerides >500 milligrams per deciliter (mg/dL) (5.7 mmol/L) at screening

W8M-MC-CWMM: Have a lifetime history of suicide attempts

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive LY3841136 and/or Tirzepatide, or placebo, for weight management

64 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY3841136
• Tirzepatide

Trial Overview The study tests LY3841136 and Tirzepatide, alone or combined, for managing weight. Some participants may receive a placebo instead to compare effects.

How Is the Trial Designed?

Group I: LY3841136 Dose 3 + Tirzepatide Dose 3 Experimental Treatment 2 Interventions

Participants will receive LY3841136 SC and Tirzepatide SC

Group II: LY3841136 Dose 3 Experimental Treatment 1 Intervention

Participants will receive LY3841136 SC

Group III: LY3841136 Dose 2 + Tirzepatide Dose 3 Experimental Treatment 2 Interventions

Participants will receive LY3841136 SC and Tirzepatide SC

Group IV: LY3841136 Dose 2 + Tirzepatide Dose 2 Experimental Treatment 2 Interventions

Participants will receive LY3841136 SC and Tirzepatide SC

Group V: LY3841136 Dose 2 + Tirzepatide Dose 1 Experimental Treatment 2 Interventions

Participants will receive LY3841136 SC and Tirzepatide SC

Group VI: LY3841136 Dose 2 Experimental Treatment 1 Intervention

Participants will receive LY3841136 SC

Group VII: LY3841136 Dose 1 + Tirzepatide Dose 1 Experimental Treatment 2 Interventions

Participants will receive LY3841136 SC and Tirzepatide SC

Group VIII: LY3841136 Dose 1 Experimental Treatment 1 Intervention

Participants will receive LY3841136 subcutaneously (SC)

Group IX: Tirzepatide Dose 3 Active Control 1 Intervention

Participants will receive Tirzepatide SC

Group X: Placebo Placebo Group 1 Intervention

Participants will receive placebo administered 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, a dual GLP-1/GIP receptor co-agonist, has been shown to significantly reduce glycosylated hemoglobin levels (1.87% to 3.02%) and body weight (5.4 to 12.9 kg) in people with type 2 diabetes over treatment periods of up to 104 weeks, demonstrating its efficacy compared to placebo and other diabetes medications.

In individuals without diabetes, tirzepatide also led to substantial weight loss (16.5% to 22.4%) over 72 weeks, indicating its potential for obesity management as well.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Type 2 Diabetes and Obesity Management. Sinha, R., Papamargaritis, D., Sargeant, JA., et al.[2023]

Tirzepatide, a new medication approved by the FDA, acts as an agonist for both GLP-1 and GIP receptors, which helps improve blood sugar control in patients with type II diabetes when combined with diet and exercise.

This drug represents a significant advancement in diabetes management, offering a new approach to treatment by targeting multiple pathways involved in glucose regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: A New Generation Therapeutic for Diabetes Type 2. Al-Horani, RA., Chedid, M.[2023]

Tirzepatide is a novel medication that acts on both GIP and GLP-1 receptors, enhancing insulin secretion and reducing glucagon levels, which helps improve glycemic control in adults with type 2 diabetes mellitus (T2DM).

It received its first approval in the USA in May 2022 for T2DM treatment and is currently being studied for additional conditions like obesity, heart failure, and non-alcoholic steatohepatitis, indicating its potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. Syed, YY.[2022]

Tirzepatide, a once-weekly medication for type 2 diabetes, not only improves blood sugar control but also leads to significant weight loss and positive changes in cardiovascular health, such as reduced blood pressure and improved insulin sensitivity.

The weight loss and metabolic benefits of tirzepatide are linked to its dual action as a GIP and GLP-1 receptor agonist, suggesting that these mechanisms play a crucial role in its effectiveness for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perspectives on weight control in diabetes - Tirzepatide. Várkonyi, TT., Pósa, A., Pávó, N., et al.[2023]

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, 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 72-week phase 3 trial involving 938 adults with obesity and type 2 diabetes, tirzepatide (10 mg and 15 mg) led to significant weight loss, with reductions of -12.8% and -14.7% respectively, compared to only -3.2% with placebo.

The safety profile of tirzepatide was generally favorable, with most adverse events being mild to moderate gastrointestinal issues, and serious adverse events were rare, indicating it is a safe option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Garvey, WT., Frias, JP., Jastreboff, AM., et al.[2023]

Tirzepatide (Mounjaro™) is a new treatment for type 2 diabetes that acts on both GIP and GLP-1 receptors, showing strong results in lowering blood glucose and promoting weight loss based on evidence from five SURPASS clinical trials.

The safety profile of tirzepatide is similar to that of existing GLP-1 receptor agonists, making it a promising option for early intervention in managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Drug: Tirzepatide (Mounjaro™). Gettman, L.[2023]

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 significantly reduces body weight in patients with type 2 diabetes and obesity, with an average weight loss of -9.81 kg compared to placebo, based on a meta-analysis of 10 studies involving 9,873 patients.

While tirzepatide is effective for weight loss, it has a higher incidence of gastrointestinal side effects compared to placebo, although serious adverse events and hypoglycemia are less common, indicating a need for monitoring these reactions during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss efficiency and safety of tirzepatide: A Systematic review. Lin, F., Yu, B., Ling, B., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06603571

NCT06603571 | A Study to Investigate Weight ... The main purpose of this study, performed under the master protocol W8M-MC-CWMM (NCT06143956), is to investigate the safety and efficacy of LY3841136 for ...

2. prnewswire.com prnewswire.com/news-releases/lillys-selective-amylin-agonist-eloralintide-demonstrated-meaningful-weight-loss-and-favorable-tolerability-in-a-phase-2-study-of-adults-with-obesity-or-overweight-302607061.html

Lilly's selective amylin agonist, eloralintide, demonstrated ... At 48 weeks, all treatment arms of eloralintide met the primary endpoint, demonstrating superior mean weight reductions from 9.5% to 20.1% ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0140673625021555

Articles Eloralintide, a selective amylin receptor agonist for ... This evidence shows that amylin receptor agonists can provide bodyweight reductions that might result in efficacy either as a monotherapy or in ...

4. appliedclinicaltrialsonline.com appliedclinicaltrialsonline.com/view/eli-lilly-trial-eloralintide-weight-reduction-adults-obesity

Eli Lilly's Phase II Trial of Eloralintide Shows Up to 20% ... Mean weight loss ranged from 9% at the lowest dose to 20% at 9 mg after 48 weeks. Placebo group saw a 0.4% mean reduction in body weight.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07215559

NCT07215559 | A Study of Macupatide (LY3532226) and ... The purpose of this study is to investigate weight reduction with macupatide and eloralintide, alone or in combination, in adult participants with obesity ...

6. withpower.com withpower.com/trial/ly3841136-tirzepatide-for-obesity-with-type-2-diabetes-f58b9

LY3841136 + Tirzepatide for Obesity with Type 2 Diabetes Tirzepatide, also known as Mounjaro, is a dual GIP and GLP-1 receptor agonist approved by the FDA in May 2022 for type 2 diabetes. Safety data from the SURPASS ...

7. thelancet.com thelancet.com/journals/lancet/article/PIIS0140-6736(25)02155-5/abstract

Eloralintide, a selective amylin receptor agonist for the ... We performed a phase 2, double blind, randomised, placebo-controlled trial with the aim of evaluating the efficacy and safety of a range of ...