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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores treatments for non-alcoholic fatty liver disease linked to obesity. Researchers aim to determine if a personalized diet plan combined with Semaglutide (a drug used to manage weight and blood sugar levels) is more effective than either option alone. Participants will join one of three groups: diet only, diet plus Semaglutide, or Semaglutide only. Individuals struggling with obesity and diagnosed with a moderate to severe fatty liver condition may be suitable candidates for this study. As an unphased trial, it offers participants the chance to contribute to innovative research that could lead to new treatment strategies.

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

Research has shown that semaglutide is generally safe and effective for treating non-alcoholic fatty liver disease (NAFLD). Studies indicate that semaglutide improves liver health and reduces liver stiffness in many patients. It also aids individuals with NAFLD and type 2 diabetes in managing their condition effectively without major side effects.

One study found that many patients experienced improved liver health without further damage when taking semaglutide. The FDA has approved semaglutide for treating serious liver diseases, indicating its safety. Overall, these findings suggest that semaglutide is a promising option for those with liver issues related to obesity, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Non-Alcoholic Fatty Liver Disease because they combine nutrition and medication in novel ways. Unlike the standard care focusing mainly on lifestyle changes and vitamin E or pioglitazone, these treatments explore the potential of semaglutide, a medication already known for treating obesity and diabetes, to work in conjunction with a personalized diet plan. Semaglutide, a GLP-1 receptor agonist, helps with weight loss, which is crucial for improving liver health. This dual approach might not only enhance weight loss but also directly target liver fat reduction, offering a fresh angle on managing this common liver condition.

What evidence suggests that this trial's treatments could be effective for hepatic steatosis associated with obesity?

This trial will evaluate the effects of different treatment approaches for non-alcoholic fatty liver disease (NAFLD). Participants in one arm will receive semaglutide, which studies have shown to improve liver function, reduce liver fat, and aid in weight loss for NAFLD patients. Research indicates that 70% of patients experienced better liver health with semaglutide, including reduced liver stiffness and scarring. Another arm will combine semaglutide with a healthy diet, which has demonstrated even greater improvements in liver health. The medication is generally well-tolerated, making it an appealing treatment option. Overall, semaglutide, especially when combined with a healthy diet, shows promise for improving liver health in individuals with obesity-related liver problems. ^{2 4 6 7 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

Capsulated probiotics consumption

Pregnancy

I have taken antibiotics in the last 3 months.

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

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]

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]

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 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9657108/

Once-Weekly Subcutaneous Semaglutide Improves Fatty ... Liver steatosis improved in most patients (70%), showing a reduction by at least one class in the semiquantitative US staging. Conclusion.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2413258

Phase 3 Trial of Semaglutide in Metabolic Dysfunction– ... A reduction in liver fibrosis without worsening of steatohepatitis was reported in 36.8% of the patients in the semaglutide group and in 22.4% ...

3. thelancet.com thelancet.com/journals/langas/article/PIIS2468-1253(23)00068-7/fulltext

Semaglutide 2·4 mg once weekly in patients with non- ... However, compared with placebo, semaglutide led to reductions in liver enzymes, liver steatosis (but not stiffness), and levels of the ...

4. hepmag.com hepmag.com/article/aasld-update-fatty-liver-disease-practice-guidance

AASLD Update Practice Guidance for Fatty Liver Disease - Hep About twice as many people taking semaglutide experienced both resolution of MASH and reduced liver fibrosis (33% versus 16%). What's more, ...

5. frontiersin.org frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2024.1343587/full

Evolving role of semaglutide in NAFLD: in combination, ... In the only available study (Arai et al., 2022), daily oral semaglutide in patients with NAFLD and T2DM given for 24 weeks improved parameters of metabolic ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9260206/

Efficacy and safety of oral semaglutide in patients with non ... In conclusion, the 24‐week oral semaglutide treatment was effective and safe in patients with NAFLD complicated by T2DM. Oral semaglutide treatment ...

7. fda.gov fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash

FDA Approves Treatment for Serious Liver Disease Known ... Interim results showed 63% of participants receiving Wegovy had MASH resolution and no worsening of liver scarring compared to 34% of ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05016882

NCT05016882 | Research Study on Whether a ... This study is being done to see if a combination of 2 medicines (called NNC0194-0499 and semaglutide) can reduce liver damage in patients with non alcoholic ...