Diet + Semaglutide for Non-Alcoholic Fatty Liver Disease

(METAfoie Trial)

Overseen By Fannie Lajeunesse-Trempe, MD., Ph.D.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Must not be taking: Antibiotics, Probiotics, others

Disqualifiers: Type 1 diabetes, Alcohol, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical trial is to improve the treatment of hepatic steatosis associated with obesity with pharmacological and nutritionnal approaches. The main question it aims to answer is: Does an individualized nutritionnal approach with a dietician combined with medication targeting obesity is the most efficient way to treat hepatic steatosis associated with obesity? Participants will either participate in one of three groups: * Nutrition: Participant will only have a regular follow-up with a registered dietician; * Nutrition + Semaglutide: Participants will start a new medication targeting obesity and will have a regular follow-up with a registered dietician; * Semaglutide: Participants will start a new medication targeting obesity.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've used obesity-targeting drugs or antibiotics in the last 3 months.

Is semaglutide safe for humans?

Research shows that semaglutide has been studied for safety in people with non-alcoholic fatty liver disease and related conditions. It is generally considered safe, but like any medication, it may have side effects, and its safety can depend on individual health conditions. ^{1 2 3 4 5}

How is the treatment with semaglutide and diet unique for non-alcoholic fatty liver disease?

This treatment is unique because semaglutide, a drug that mimics a hormone called GLP-1, helps with weight loss and blood sugar control, which can be beneficial for non-alcoholic fatty liver disease. Currently, there are no approved drugs specifically for this condition, making this combination of diet and semaglutide a novel approach. ^{1 3 4 6 7}

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

Research shows that semaglutide, a drug originally used for diabetes, can help reduce liver fat and improve liver health in people with non-alcoholic fatty liver disease. It also aids in weight loss, which is beneficial for managing this condition. ^{1 2 3 4 8}

Who Is on the Research Team?

Fannie Lajeunesse-Trempe, MD., Ph.D.

Principal Investigator

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec - Université Laval

Are You a Good Fit for This Trial?

This trial is for individuals with fatty liver disease linked to diabetes, obesity, or non-alcoholic causes. Participants should be willing to follow a diet plan or take a medication called semaglutide, or both. The study excludes details on specific inclusion and exclusion criteria.

Inclusion Criteria

My liver has moderate to severe fat buildup.

Body mass index between 30 and 50 kg/m2

Exclusion Criteria

I have taken antibiotics in the last 3 months.

Capsulated probiotics consumption

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either nutritional counseling, Semaglutide therapy, or a combination of both for the management of hepatic steatosis associated with obesity

12 months

4 visits (in-person) at 0, 3, 6, and 12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Diet
• Semaglutide

Trial Overview The trial tests if combining an individualized diet plan from a dietician with semaglutide (a drug targeting obesity) is more effective in treating fatty liver associated with obesity than either approach alone. There are three groups: diet only, diet plus semaglutide, and semaglutide only.

How Is the Trial Designed?

Group I: Nutrition Active Control 1 Intervention

This arm will only participate in an individualized nutritionnal approach.

Group II: Nutrition + Semaglutide Active Control 2 Interventions

This arm will initiate a pharmacological intervention to treat obesity (Semaglutide) and will participate in an individualized nutritionnal approach.

Group III: Semaglutide Active Control 1 Intervention

This arm will only initiate a pharmacological intervention to treat obesity (Semaglutide)

Who Is Running the Clinical Trial?

Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Lead Sponsor

Trials

26

Recruited

6,300+

Published Research Related to This Trial

In a systematic review of 8 studies involving 2413 patients, 24 weeks of semaglutide treatment significantly reduced liver enzymes (alanine transaminase and aspartate transaminase) and improved liver fat content and stiffness, indicating its efficacy in treating non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH).

Despite its benefits, semaglutide treatment was associated with a higher risk of serious gastrointestinal adverse events, such as nausea and vomiting, highlighting the need for careful monitoring of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Das, S., Samajdar, SS., et al.[2023]

In a 24-week pilot study involving 16 patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, oral semaglutide significantly improved liver function, reduced body weight, and lowered triglyceride levels.

The treatment was associated with a decrease in insulin resistance and hepatic steatosis, with most side effects being mild gastrointestinal issues, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study. Arai, T., Atsukawa, M., Tsubota, A., et al.[2022]

Semaglutide significantly improves key indicators of non-alcoholic fatty liver disease (NAFLD), including the likelihood of non-alcoholic steatohepatitis (NASH) resolution and reductions in liver stiffness and liver enzymes, based on a meta-analysis of three randomized controlled trials involving 458 patients.

While semaglutide is effective in treating NAFLD and also promotes weight loss and better glycemic control, it does increase gastrointestinal side effects, although the overall risk of serious adverse events remains similar to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide in non-alcoholic fatty liver disease. Zhu, K., Kakkar, R., Chahal, D., et al.[2023]

In a phase 2 trial involving 71 patients with NASH-related cirrhosis, semaglutide did not significantly improve liver fibrosis or lead to NASH resolution compared to placebo after 48 weeks.

The safety profile of semaglutide was similar to that of the placebo, with no new safety concerns identified, and common side effects included nausea and diarrhea, but overall liver and kidney function remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Loomba, R., Abdelmalek, MF., Armstrong, MJ., et al.[2023]

In a study of 213 patients with type 2 diabetes, weekly subcutaneous semaglutide significantly reduced biomarkers of metabolic-associated fatty liver disease (MAFLD), specifically the hepatic steatosis index (HSI) and fibrosis-4 (FIB-4) index, over 24 weeks.

The improvements in liver health were primarily linked to weight loss and reductions in triglyceride levels and insulin resistance, indicating that semaglutide's benefits extend beyond just controlling blood sugar levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity. Carretero-Gómez, J., Carrasco-Sánchez, FJ., Fernández-Rodríguez, JM., et al.[2023]

In a study using Ldlr-/-.Leiden mice, semaglutide significantly reduced liver fat and inflammation by 74% and 73% respectively, indicating its potential effectiveness in treating non-alcoholic steatohepatitis (NASH).

While semaglutide improved liver health by reversing certain gene expressions associated with NASH, it did not significantly affect liver fibrosis, suggesting that it may need to be combined with other treatments for advanced fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. Inia, JA., Stokman, G., Morrison, MC., et al.[2023]

In a phase II trial involving 108 patients with non-alcoholic steatohepatitis (NASH), the combination of semaglutide with cilofexor and/or firsocostat was found to be safe and well tolerated, with similar rates of adverse events across treatment groups.

The combination therapies resulted in greater improvements in liver steatosis and liver biochemistry compared to semaglutide alone, suggesting that targeting multiple mechanisms may enhance treatment efficacy for NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. Alkhouri, N., Herring, R., Kabler, H., et al.[2022]

Semaglutide treatment in obese mice led to significant weight loss and improvements in metabolic health, including better glucose tolerance, reduced insulin resistance, and lower liver inflammation, indicating its efficacy as a GLP-1 receptor agonist.

The study found that Semaglutide's benefits on liver health and metabolic markers were not solely due to weight loss, as it also directly improved glucose uptake and reduced endoplasmic reticulum stress, highlighting its potential mechanisms of action beyond just weight reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obese mice weight loss role on nonalcoholic fatty liver disease and endoplasmic reticulum stress treated by a GLP-1 receptor agonist. Pontes-da-Silva, RM., de Souza Marinho, T., de Macedo Cardoso, LE., et al.[2022]

Citations

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

Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. [2023]

2. Australia pubmed.ncbi.nlm.nih.gov

Efficacy and safety of oral semaglutide in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study. [2022]

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

Efficacy and safety of semaglutide in non-alcoholic fatty liver disease. [2023]

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

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. [2023]

5. Spain pubmed.ncbi.nlm.nih.gov

Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Semaglutide Has Beneficial Effects on Non-Alcoholic Steatohepatitis in Ldlr-/-.Leiden Mice. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and efficacy of combination therapy with semaglutide, cilofexor and firsocostat in patients with non-alcoholic steatohepatitis: A randomised, open-label phase II trial. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Obese mice weight loss role on nonalcoholic fatty liver disease and endoplasmic reticulum stress treated by a GLP-1 receptor agonist. [2022]