Tirzepatide for Non-alcoholic Fatty Liver Disease

(SYNERGY-NASH Trial)

Recruiting at 233 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

190 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial is testing if a medication called tirzepatide, taken regularly, is safe and effective for people with Nonalcoholic Steatohepatitis (NASH). NASH is a liver condition that can be hard to treat. Tirzepatide helps control blood sugar and reduce fat in the liver, which may improve liver health. Tirzepatide has shown effectiveness in treating obesity and diabetes.

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 tirzepatide safe for humans?

Tirzepatide is generally considered safe for humans, with the most common side effects being mild to moderate stomach-related issues like nausea and diarrhea. It has been approved for type 2 diabetes treatment in the US and other regions, and its safety profile is similar to other drugs in its class. ^{1 2 3 4 5}

How is the drug tirzepatide unique for treating non-alcoholic fatty liver disease?

Tirzepatide is unique because it combines two actions in one drug, targeting both GIP and GLP-1 receptors, which helps control blood sugar and reduce liver fat. It is administered as a once-weekly injection, making it more convenient compared to daily treatments. ^{1 2 3 6 7}

What data supports the effectiveness of the drug Tirzepatide for treating non-alcoholic fatty liver disease?

Research shows that drugs similar to Tirzepatide, which target specific receptors in the body, have been effective in reducing liver fat and improving liver health in people with non-alcoholic fatty liver disease. Additionally, Tirzepatide has shown promise in reducing liver fat content in people with type 2 diabetes, suggesting it may also be beneficial for non-alcoholic fatty liver disease. ^{2 3 5 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

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]

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]

Citations

1. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Hepatic Impairment on the Pharmacokinetics of the Dual GIP and GLP-1 Receptor Agonist Tirzepatide. [2022]

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

Effects of Novel Dual GIP and GLP-1 Receptor Agonist Tirzepatide on Biomarkers of Nonalcoholic Steatohepatitis in Patients With Type 2 Diabetes. [2021]

3. Switzerland 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. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Mechanisms and possible hepatoprotective effects of glucagon-like peptide-1 receptor agonists and other incretin receptor agonists in non-alcoholic fatty liver disease. [2023]

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

Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Tirzepatide: First Approval. [2022]

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

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Focus on tirzepatide, a dual unimolecular GIP-GLP-1 receptor agonist in type 2 diabetes]. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. [2022]