Tirzepatide for Non-alcoholic Fatty Liver Disease

(SYNERGY-NASH Trial)

No longer recruiting at 239 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

Disqualifiers: Alcohol abuse, Cirrhosis, Heart attack, Cancer, others

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests tirzepatide, a medication administered weekly, to evaluate its efficacy and safety in treating Nonalcoholic Steatohepatitis (NASH), a liver condition. Participants will receive either a placebo or one of three doses of tirzepatide. The trial suits individuals with a body mass index (BMI) between 27 and 50, diagnosed with NASH, who have stable weight and are willing to undergo liver biopsies. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that participants with type 2 diabetes can join if their HbA1c is ≤9.5%, which might imply that some diabetes medications are allowed.

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

Research has shown that tirzepatide, the treatment under study, has generally been well-tolerated in past studies. In these studies, patients using tirzepatide demonstrated improvements in markers related to liver health, suggesting potential liver benefits.

Tirzepatide also aids in weight loss and improves liver health in conditions like Type 2 diabetes. This is significant because excess weight often correlates with liver problems. Researchers have studied the safety of tirzepatide in various contexts, and while all medications can have side effects, no major safety issues have consistently emerged with this drug.

This trial is in Phase 2, indicating that tirzepatide has already passed initial safety checks in earlier studies. This phase further evaluates its safety and effectiveness for individuals with liver-related issues, such as those with NASH. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Tirzepatide is unique because it targets both the GLP-1 and GIP receptors, unlike most current treatments for non-alcoholic fatty liver disease (NAFLD) that primarily focus on lifestyle changes or medications addressing only one pathway. This dual-action mechanism is exciting because it may offer enhanced benefits in reducing liver fat and improving metabolic health. Additionally, tirzepatide is administered through a simple weekly injection, which could improve patient adherence compared to more complex treatment regimens.

What evidence suggests that tirzepatide might be an effective treatment for NASH?

Research has shown that tirzepatide, a type of medication, could help treat non-alcoholic fatty liver disease (NAFLD). Studies suggest it may reduce fat buildup in the liver and improve liver function. This is important because less liver fat can enhance overall liver health. Tirzepatide also aids in weight loss, which benefits individuals with NAFLD, as losing weight can improve liver health. Additionally, it treats type 2 diabetes and obesity, conditions often linked to liver problems. Overall, these findings suggest tirzepatide could be a promising treatment option for NAFLD. ^{2 6 7 8 9}

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 Nonalcoholic Steatohepatitis (NASH) who have a BMI of 27-50, stable weight for the past 3 months, and if diabetic, controlled HbA1c levels. They must not have had recent severe cardiovascular events or active cancer in the last 5 years and should be willing to undergo liver biopsies.

Inclusion Criteria

Participants must have histologic diagnosis of NASH with stage 2 or 3 fibrosis by liver biopsy

Participants must have a body mass index (BMI) ≥27 kilograms per square meter (kg/m²) and ≤50 kg/m² with stable body weight for at least 3 months

If with T2DM, hemoglobin A1c (HbA1c) ≤9.5%

Exclusion Criteria

Participant must not have family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma (family is defined as a first degree relative)

Participants must not have a diagnosis of type 1 diabetes

Female participants must not be pregnant, breast-feeding, or intend to become pregnant or of childbearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tirzepatide or placebo administered subcutaneously once a week

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Tirzepatide

Trial Overview The study tests Tirzepatide's safety and effectiveness against NASH. Participants will receive either Tirzepatide or a placebo once weekly. The trial includes people with varying stages of fibrosis due to NASH, some may also have type 2 diabetes.

How Is the Trial Designed?

Group I: 5 mg Tirzepatide Experimental Treatment 1 Intervention

5 milligrams (mg) tirzepatide administered subcutaneously (SC) once a week.

Group II: 15 mg Tirzepatide Experimental Treatment 1 Intervention

15 mg tirzepatide administered SC once a week.

Group III: 10 mg Tirzepatide Experimental Treatment 1 Intervention

10 mg tirzepatide administered SC once a week.

Group IV: Placebo Placebo Group 1 Intervention

Placebo administered SC once a week.

Tirzepatide is already approved in United States, European Union, Canada, United Kingdom for the following indications:

Approved in United States as Mounjaro for:

• Type 2 diabetes

Approved in European Union as Mounjaro for:

• Type 2 diabetes

Approved in Canada as Mounjaro for:

• Type 2 diabetes

Approved in United States as Zepbound for:

• Weight loss
• Moderate to severe obstructive sleep apnea

Approved in United Kingdom as Zepbound for:

• Weight loss

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 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 novel GLP-1 receptor agonist, has been shown to significantly reduce A1C levels and body weight in patients with type 2 diabetes compared to placebo and other active treatments.

The safety profile of tirzepatide is similar to other GLP-1 receptor agonists, with the most common side effects being mild to moderate gastrointestinal issues, and it does not increase the risk of hypoglycemia, making it a promising treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. Kushner, P., Anderson, JE., Simon, J., et al.[2023]

A systematic review of 11 randomized controlled trials involving 936 middle-aged individuals found that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) significantly reduced liver fat content and serum liver enzyme levels in patients with nonalcoholic fatty liver disease (NAFLD) or steatohepatitis (NASH) over a median treatment duration of 26 weeks.

GLP-1 RAs, particularly liraglutide and semaglutide, also showed greater histological resolution of NASH without worsening liver fibrosis, indicating their potential as effective treatments for these liver conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide-1 Receptor Agonists for Treatment of Nonalcoholic Fatty Liver Disease and Nonalcoholic Steatohepatitis: An Updated Meta-Analysis of Randomized Controlled Trials. Mantovani, A., Petracca, G., Beatrice, G., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9865319/

GLP-1 Receptor Agonists in Non-Alcoholic Fatty Liver Disease To date, the only treatment proved to be effective in NAFLD is a weight loss of ≥7–10%, able to significantly improve the histological grade of fibrosis and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12361993/

Tirzepatide, a dual GIP/GLP-1 receptor agonist, alleviates ... These results suggest that tirzepatide may be an effective treatment for MASLD by reducing liver fat accumulation and modulating lipid ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2206038

Tirzepatide Once Weekly for the Treatment of Obesity These improvements may translate to reduced risk of cardiovascular disease, chronic kidney disease, nonalcoholic fatty liver disease, and type 2 ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03131687

NCT03131687 | A Study of Tirzepatide (LY3298176) in ... The purpose of this study is to evaluate the efficacy of the study drug tirzepatide in participants with type 2 diabetes mellitus. Official Title. A Phase 2 ...

5. aasld.org aasld.org/liver-fellow-network/core-series/why-series/why-are-glp-1-agonists-being-used-treat-patients

Why are GLP-1 agonists being used to treat patients with ... GLP-1 agonists are approved for the treatment of diabetes and for obesity. Why are patients with non-alcoholic fatty liver disease (NAFLD) suddenly being ...

6. nejm.org nejm.org/doi/full/10.1056/NEJMoa2401943

Tirzepatide for Metabolic Dysfunction–Associated ... Key exclusion criteria were chronic liver disease other than MASH, cirrhosis, evidence of hepatic decompensation, excessive alcohol consumption ...

7. diabetesjournals.org diabetesjournals.org/care/article/43/6/1352/35649/Effects-of-Novel-Dual-GIP-and-GLP-1-Receptor

Effects of Novel Dual GIP and GLP-1 Receptor Agonist ... In post hoc analyses, higher tirzepatide doses significantly decreased NASH-related biomarkers and increased adiponectin in patients with T2DM.

8. wjgnet.com wjgnet.com/1007-9327/full/v31/i37/111435.htm

Efficacy and safety of anti-obesity drugs in metabolic ... Efficacy and safety of anti-obesity drugs in metabolic dysfunction-associated steatotic liver disease: An updated review.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2352304225002508

Tirzepatide, a dual GIP/GLP-1 receptor agonist, alleviates ... Data analysis was performed using GraphPad Prism 10.0. Results. Tirzepatide alleviates lipid accumulation in the livers of MASLD mice. To determine whether ...