Efinopegdutide for Fatty Liver Disease

Recruiting at 39 trial locations

Overseen By Toll Free Number

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Merck Sharp & Dohme LLC

Must be taking: Oral antihyperglycemics

Disqualifiers: Chronic liver disease, Pancreatitis, T1DM, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 weeks

129 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This study will evaluate the effect of efinopegdutide administration once every 2 weeks (Q2W) versus once weekly (Q1W) on mean relative reduction from baseline in liver fat content (LFC) after 28 weeks, as well as the safety and tolerability of the different regimens of efinopegdutide.

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

The trial does not specify if you need to stop your current medications. However, if you have type 2 diabetes, your condition must be controlled by diet or stable doses of oral medications.

Is efinopegdutide safe for humans?

Efinopegdutide has been studied for its safety in patients with non-alcoholic fatty liver disease, and its safety profile was found to be comparable to other similar treatments. While specific safety data for efinopegdutide is limited, related treatments in the same class have shown a generally acceptable safety profile in clinical trials. ^{1 2 3 4 5}

What makes the drug Efinopegdutide unique for treating fatty liver disease?

Efinopegdutide is unique because it targets both the GLP-1 and glucagon receptors, potentially offering more comprehensive benefits for fatty liver disease by reducing liver fat content and improving liver function, unlike treatments that target only one receptor. ^{1 2 3 5 6}

What data supports the effectiveness of the drug Efinopegdutide for treating fatty liver disease?

Research shows that drugs similar to Efinopegdutide, which target the same receptors, have been effective in reducing liver fat and improving liver health in patients with fatty liver disease. Specifically, studies on GLP-1 receptor agonists like semaglutide have shown significant reductions in liver fat content and improvements in liver enzyme levels. ^{1 2 5 7 8}

Who Is on the Research Team?

Medical Director

Principal Investigator

Merck Sharp and Dohme LLC

Are You a Good Fit for This Trial?

This trial is for adults with metabolic dysfunction-associated steatotic liver disease (MASLD), which includes conditions like fatty liver disease and non-alcoholic fatty liver disease. Participants should have a certain level of fat in their livers but otherwise be generally healthy.

Inclusion Criteria

I either don't have type 2 diabetes, or if I do, it's well-controlled with diet or medication.

Has body mass index (BMI) ≥25 kg/m^2 (≥23 kg/m^2 for Asian participants) AND has stable weight, defined as ≤5% gain or loss of body weight for at least 3 months before screening

Exclusion Criteria

I haven't had major heart or stroke issues in the last 6 months.

I have had pancreatitis before.

I have a history of type 1 diabetes, diabetic ketoacidosis, or diabetes due to pancreas surgery.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive efinopegdutide via subcutaneous injection in a dose-escalating regimen for 28 weeks

28 weeks

Bi-weekly or weekly visits depending on dosing regimen

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Efinopegdutide

Trial Overview The study is testing the drug efinopegdutide, given as an injection. It will compare two dosing schedules: once every two weeks (Q2W) versus once weekly (Q1W). The focus is on how well each schedule reduces liver fat content over 28 weeks and how safe and tolerable they are.

How Is the Trial Designed?

Group I: Efinopegdutide Q2W 15 mg Experimental Treatment 1 Intervention

Participants will receive efinopegdutide Q2W via SC injection for 28 weeks in a dose-escalating regimen of 2 mg for 4 weeks, 4 mg for 4 weeks, 7 mg for 4 weeks, 10 mg for 4 weeks, and 15 mg for up to 12 weeks.

Group II: Efinopegdutide Q2W 10 mg Experimental Treatment 1 Intervention

Participants will receive efinopegdutide Q2W via SC injection for 28 weeks in a dose-escalating regimen of 2 mg for 4 weeks, 4 mg for 4 weeks, 7 mg for 4 weeks, and 10 mg for up to 16 weeks.

Group III: Efinopegdutide Q1W 10 mg Active Control 1 Intervention

Participants will receive efinopegdutide Q1W via subcutaneous (SC) injection for 28 weeks in a dose-escalating regimen of 2 mg for 4 weeks, 4 mg for 4 weeks, 7 mg for 4 weeks, and 10 mg for up to 16 weeks.

Who Is Running the Clinical Trial?

Merck Sharp & Dohme LLC

Lead Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

In a phase IIa study involving 145 participants with non-alcoholic fatty liver disease (NAFLD), efinopegdutide (10 mg weekly) resulted in a significantly greater reduction in liver fat content (LFC) compared to semaglutide (1 mg weekly), with reductions of 72.7% and 42.3% respectively after 24 weeks (p < 0.001).

Both treatments led to weight loss, with efinopegdutide showing an 8.5% reduction compared to 7.1% for semaglutide, although efinopegdutide was associated with slightly higher gastrointestinal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. Romero-Gómez, M., Lawitz, E., Shankar, RR., et al.[2023]

In a study involving 10 non-diabetic patients with non-alcoholic fatty liver disease (NAFLD) and 10 matched controls, GLP-1 infusion effectively suppressed glucagon levels in both groups, indicating that the glucagon-suppressive effect of GLP-1 is preserved in NAFLD patients.

Despite the presence of fasting hyperglucagonaemia in NAFLD patients, GLP-1 did not affect endogenous glucose production, suggesting that while GLP-1 enhances insulin secretion in these patients, it does not alter glucose output from the liver.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease. Junker, AE., Gluud, LL., van Hall, G., et al.[2018]

GLP-1 receptor agonists (GLP-1RA) significantly reduce liver enzymes such as alanine transaminase (ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in patients with nonalcoholic fatty liver disease (NAFLD), based on a meta-analysis of 12 studies involving 677 subjects.

However, GLP-1RA treatment does not significantly affect the lipid profile, including triglycerides, total cholesterol, high-density lipoprotein (HDL), or low-density lipoprotein (LDL), indicating that while they help with liver health, they do not improve lipid levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 Receptor Agonist Effects on Lipid and Liver Profiles in Patients with Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. Rezaei, S., Tabrizi, R., Nowrouzi-Sohrabi, P., et al.[2021]

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]

In a phase 2a trial involving men and women with overweight or obesity and type 2 diabetes, cotadutide significantly reduced liver glycogen and fat compared to both placebo and liraglutide, indicating its efficacy in improving liver health.

The safety and tolerability of cotadutide were found to be comparable to previous studies, suggesting it is a safe option for treating conditions like non-alcoholic steatohepatitis and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. Parker, VER., Robertson, D., Erazo-Tapia, E., et al.[2023]

Liraglutide effectively prevents the development of insulin resistance and non-alcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet, demonstrating its potential as a protective treatment against these conditions.

The mechanism of action involves the inhibition of the MKK4/JNK signaling pathway, leading to reduced inflammation and improved insulin sensitivity, as indicated by decreased levels of proinflammatory cytokines and lipogenesis-related genes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK. Zhang, L., Yang, M., Ren, H., et al.[2015]

Liraglutide, a GLP-1 analogue, has shown safety and efficacy in treating two adolescent females with type II diabetes and biopsy-proven nonalcoholic steatohepatitis (NASH), leading to weight loss and improved liver enzymes.

This case series suggests that liraglutide could be a beneficial treatment option for pediatric patients with obesity, NAFLD, and T2DM, especially when lifestyle interventions are ineffective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide with Lifestyle Intervention in Adolescents with Overweight/Obesity, Nonalcoholic Fatty Liver Disease, and Type II Diabetes Mellitus. Kohut, T., Panganiban, J.[2023]

Cotadutide, a GLP-1R/GcgR agonist, effectively reduces body weight, food intake, and improves glucose control primarily through GLP-1 signaling, while its beneficial effects on liver health are mediated by Gcg signaling, as shown in preclinical studies.

In comparison to other treatments like Liraglutide and Obeticholic acid, Cotadutide demonstrated a greater ability to alleviate liver fibrosis in mouse models of non-alcoholic steatohepatitis (NASH), highlighting its potential as a promising therapeutic option for liver diseases associated with obesity and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis. Boland, ML., Laker, RC., Mather, K., et al.[2021]

Citations

1. Netherlands pubmed.ncbi.nlm.nih.gov

A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of glucagon-like peptide-1 on glucagon secretion in patients with non-alcoholic fatty liver disease. [2018]

3. Egypt pubmed.ncbi.nlm.nih.gov

GLP-1 Receptor Agonist Effects on Lipid and Liver Profiles in Patients with Nonalcoholic Fatty Liver Disease: Systematic Review and Meta-Analysis. [2021]

4. 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]

5. Germany pubmed.ncbi.nlm.nih.gov

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. [2023]

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

GLP-1 analogue prevents NAFLD in ApoE KO mice with diet and Acrp30 knockdown by inhibiting c-JNK. [2015]

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

Liraglutide with Lifestyle Intervention in Adolescents with Overweight/Obesity, Nonalcoholic Fatty Liver Disease, and Type II Diabetes Mellitus. [2023]

8. Germany pubmed.ncbi.nlm.nih.gov

Resolution of NASH and hepatic fibrosis by the GLP-1R/GcgR dual-agonist Cotadutide via modulating mitochondrial function and lipogenesis. [2021]