Tirzepatide + Retatrutide for Fatty Liver Disease

Recruiting at 551 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Eli Lilly and Company

Disqualifiers: Other liver disease, BMI <25, Decompensated liver, Weight loss, HbA1c >10%, Type 1 diabetes

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 25

Duration: 224 weeks

4500 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether two new treatments, retatrutide and tirzepatide, can prevent serious liver problems in people with fatty liver disease linked to metabolism issues. The goal is to determine if these treatments can stop major liver issues in those at high risk. Participants will receive either one of the new treatments or a placebo (a non-active substance) to compare results. The trial seeks adults with fatty liver disease, identified by specific non-invasive tests, who have not had other types of liver disease. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

In earlier studies, retatrutide demonstrated a safety profile similar to other hormone-based treatments. Most participants tolerated it well, without serious liver problems or other severe side effects. It was tested in groups with obesity and liver disease, and no major safety concerns emerged.

For tirzepatide, studies have also shown it is well-tolerated. It improved liver health and weight without causing serious issues. Participants using tirzepatide did not report major liver problems, and it improved liver-related tests.

Both treatments are being tested for fatty liver disease. Their safety in humans appears promising based on past research. However, as with any treatment, individual experiences can vary. Always consult a doctor about potential risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about retatrutide and tirzepatide for treating fatty liver disease because these drugs offer a fresh approach compared to the current standard options like lifestyle changes, vitamin E, or pioglitazone. Both drugs are GLP-1 receptor agonists, but they have unique features: tirzepatide also acts as a GIP receptor agonist, while retatrutide targets the glucagon receptor, potentially offering enhanced metabolic effects. These mechanisms could improve liver health by better regulating glucose and lipid metabolism, potentially addressing the root causes of fatty liver disease more effectively than existing treatments.

What evidence suggests that this trial's treatments could be effective for fatty liver disease?

Research has shown that retatrutide, one of the treatments in this trial, can greatly reduce liver fat in people with fatty liver disease. In one study, 9 out of 10 patients had normal liver fat levels after 48 weeks of treatment. Another study found an 86% decrease in liver fat in those taking the highest dose of retatrutide.

For tirzepatide, another treatment option in this trial, studies have demonstrated its effectiveness in lowering liver fat. After a year of treatment, patients experienced a dose-dependent reduction in liver fat—higher doses led to greater reductions. Tirzepatide is also associated with weight loss and improved liver health markers. Both treatments show promising potential for helping people with fatty liver disease. ^{1 2 3 5 6}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

Adults with high-risk metabolic dysfunction-associated steatotic liver disease (MASLD) are eligible for this trial. They must have a likelihood of developing major adverse liver outcomes as indicated by non-invasive tests. Key exclusions include other significant medical conditions, participation in other studies, or factors that may interfere with the study.

Inclusion Criteria

Have ELF score of ≥9 and ≤10.8 at screening

Have VCTE LSM ≥10 kilopascal (kPa) and <20 kPa at screening

My liver fat content is 8% or higher.

Exclusion Criteria

Have a body mass index (BMI) <25 kilogram per square meter (kg/m2)

Have a hemoglobin A1c (HbA1c) greater than 10%

I do not have any liver disease other than MASLD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either retatrutide, tirzepatide, or placebo to assess prevention of major adverse liver outcomes

224 weeks

25 to 30 clinic visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Eligible participants may continue to receive retatrutide or tirzepatide for an additional 2 years

104 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Retatrutide
• Tirzepatide

Trial Overview The SYNERGY-OUTCOMES trial is testing whether retatrutide and tirzepatide can prevent serious liver problems in people with MASLD. Participants will be randomly assigned to receive either one of these drugs or a placebo over approximately 224 weeks, involving up to 30 clinic visits.

How Is the Trial Designed?

Group I: Tirzepatide (TZ01) Experimental Treatment 1 Intervention

Participants will receive tirzepatide subcutaneously (SC)

Group II: Retatrutide (RT01) Experimental Treatment 1 Intervention

Participants will receive retatrutide SC

Group III: Placebo (RT01) Placebo Group 1 Intervention

Participants will receive placebo SC

Group IV: Placebo (TZ01) Placebo Group 1 Intervention

Participants will receive placebo 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

Citations

1. nature.com nature.com/articles/s41591-024-03018-2

Triple hormone receptor agonist retatrutide for metabolic ... Liver fat reduction of at least 50% and at least 70% was achieved by 43–100% and 32–93% of participants who received retatrutide, respectively ( ...

2. diabetes.org diabetes.org/newsroom/american-diabetes-association-highlights-novel-agent-retatrutide-results-substantial-weight-reduction-people-with-obesity-type-2-diabetes-during-late-breaking-symposium

San Diego, California Findings showed that in those with NAFLD, the amount of fat in the liver normalized in 9 out of 10 patients after 48 weeks treatment with the ...

3. adameetingnews.org adameetingnews.org/phase-2-trial-results-demonstrate-benefits-of-retatrutide-in-obesity-type-2-diabetes-nash/

Phase 2 trial results demonstrate benefits of retatrutide in ... “At the highest dose of retatrutide, more than 90% of participants with obesity and NAFLD achieved normalization of liver fat. This suggests ...

4. statnews.com statnews.com/2023/06/26/eli-lilly-fatty-liver-disease-retatrutide-obesity-drug/

Fatty liver disease was alleviated by Lilly's 'triple-G' obesity drug Among 98 patients with nonalcoholic fatty liver disease, those on the highest dose tested of the drug, retatrutide, experienced an 86% decrease ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa2301972

Triple–Hormone-Receptor Agonist Retatrutide for Obesity In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight.

6. gertitashkomd.com gertitashkomd.com/dr-tashkos-key-clinical-trials-retatrutide-fatty-liver/

Retatrutide: A Promising Breakthrough for Fatty Liver Disease Dr. Tashko reviews a Nature study on Retatrutide, showcasing its potential as a groundbreaking treatment for fatty liver disease.