Semaglutide for Non-Alcoholic Fatty Liver Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Must not be taking: Atypical neuroleptics, Insulin, others
Disqualifiers: Pregnancy, Hepatitis, HIV, others
No Placebo Group
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?Background:
In non-alcoholic fatty liver disease (NAFLD), fat accumulates in the liver and can cause damage. Researchers want to learn what causes the damage NAFLD, and to see if a medication can help.
Objective:
To find out how the liver in people with NAFLD responds to feeding, and how this relates to their response to the drug semaglutide.
Eligibility:
People with NAFLD and healthy volunteers ages 18 and older
Design:
Participants will be screened with:
Medical history
Physical exam
Blood tests
Imaging: A machine will take pictures of the participant s body.
Within 2-8 weeks of enrollment, participants will stay in the clinic for several days. This includes:
Blood, urine, heart, and imaging tests
For NAFLD participants only: A needle-like device will remove a small biopsy of the liver and fatty tissue.
Participants will be alone in a special room for 5 hours. They will breathe through a tube under the nostrils. They will have blood drawn several times.
The baseline visit concludes participation for healthy volunteers but NAFLD participants will contine.
About 6 weeks after discharge, participants will stay in the clinic again and repeat the tests. They will get their first semaglutide dose by injection.
Participants will have visits weeks 1, 2, 4, 8, 12, 16, 20, and 24 of treatment. Visits include blood tests.
Participants will inject semaglutide once a week at home.
At week 30, participants will stay in the clinic again and repeat the tests.
Participants will have a final visit 12 weeks after stopping treatment. This includes blood and urine tests.
...
Will I have to stop taking my current medications?
The trial protocol does not specify if you must stop taking your current medications. However, certain medications, especially those for diabetes or those known to cause fatty liver disease, may need to be stopped or adjusted before enrollment. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the drug semaglutide for treating non-alcoholic fatty liver disease?
Research shows that semaglutide can lead to significant weight loss and improve liver health in patients with non-alcoholic fatty liver disease (NAFLD). It is also noted for resolving non-alcoholic steatohepatitis (NASH), a more severe form of NAFLD, making it a promising option for these conditions.
12345Is semaglutide safe for humans?
Research shows that semaglutide, used under names like Ozempic, Wegovy, and Rybelsus, has been studied for safety in conditions like non-alcoholic fatty liver disease and diabetes. These studies generally support its safety, but as with any medication, there may be side effects, so it's important to discuss with a healthcare provider.
23467How is the drug semaglutide unique for treating non-alcoholic fatty liver disease?
Semaglutide is unique because it not only improves liver health but also helps with weight loss and resolves non-alcoholic steatohepatitis (NASH), which is not achieved by other treatments like obeticholic acid. Additionally, semaglutide is considered safer and more effective in reducing liver fat and improving liver enzymes compared to other available options.
24568Eligibility Criteria
Adults aged 18+ with Non-Alcoholic Fatty Liver Disease (NAFLD) can join this trial. They must have a certain level of liver fat and no recent significant alcohol consumption. Exclusions include pregnancy, breastfeeding, other liver diseases, uncontrolled diabetes or thyroid issues, severe kidney disease, specific medication use within the last 3 months, and inability to undergo MRI or biopsy.Inclusion Criteria
I have a fatty liver with a fat content of 10% or more.
Ability of subject to understand and the willingness to sign a written informed consent document
I am 18 years old or older.
+2 more
Exclusion Criteria
I am HIV positive.
My thyroid condition is not under control.
I am currently taking orlistat.
+29 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-8 weeks
1 visit (in-person)
Baseline Assessment
Participants undergo initial assessments including blood, urine, heart, and imaging tests. NAFLD participants receive liver and fatty tissue biopsies.
Several days
In-clinic stay
Treatment
Participants receive semaglutide injections weekly for 30 weeks. Visits occur at weeks 1, 2, 4, 8, 12, 16, 20, and 24 for blood tests.
30 weeks
8 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, including a final visit 12 weeks after stopping treatment with blood and urine tests.
12 weeks
1 visit (in-person)
Participant Groups
The trial is testing how Semaglutide affects the liver's response to sugar in people with NAFLD. Participants will undergo tests including blood work and imaging before and after receiving Semaglutide injections for up to 24 weeks at home followed by additional clinic visits.
3Treatment groups
Experimental Treatment
Active Control
Group I: Arm B: NASHExperimental Treatment1 Intervention
Participants with NASH on baseline biopsy
Group II: Arm A: SteatosisExperimental Treatment1 Intervention
Participants with steatosis on baseline biopsy
Group III: Arm C: HealthyActive Control1 Intervention
Healthy Volunteers
Semaglutide is already approved in European Union, United States, Canada, Japan, United States, United States for the following indications:
🇪🇺 Approved in European Union as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇺🇸 Approved in United States as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇨🇦 Approved in Canada as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇯🇵 Approved in Japan as Ozempic for:
- Type 2 diabetes
- Cardiovascular disease
- Obesity
🇺🇸 Approved in United States as Wegovy for:
- Obesity
🇺🇸 Approved in United States as Rybelsus for:
- Type 2 diabetes
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
Loading ...
Who Is Running the Clinical Trial?
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Lead Sponsor
National Cancer Institute (NCI)Collaborator
References
Obese mice weight loss role on nonalcoholic fatty liver disease and endoplasmic reticulum stress treated by a GLP-1 receptor agonist. [2022]The weight loss following Semaglutide treatment, a GLP-1 receptor agonist, might be responsible for some effects observed on the nonalcoholic fatty liver disease of obese mice.
Role of semaglutide in the treatment of nonalcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. [2023]This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of 24 weeks of semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).
Efficacy and safety of semaglutide in non-alcoholic fatty liver disease. [2023]Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower health-related quality of life. To date, there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis (NASH). Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD.
Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. [2023]Patients with non-alcoholic steatohepatitis (NASH)-related cirrhosis are at high risk of liver-related and all-cause morbidity and mortality. We investigated the efficacy and safety of the glucagon-like peptide-1 analogue semaglutide in patients with NASH and compensated cirrhosis.
Comparing the Efficacy and Safety of Obeticholic Acid and Semaglutide in Patients With Non-Alcoholic Fatty Liver Disease: A Systematic Review. [2022]Patients with non-alcoholic fatty liver disease (NAFLD) have an increased risk of developing progressive fibrosis, cirrhosis, and hepatocellular carcinoma. As of now, there are no FDA-approved treatments for NAFLD/non-alcoholic steatohepatitis (NASH) or its associated fibrosis. Although many drugs are under clinical trial, both obeticholic acid (OCA) and semaglutide are among the few that have reached phase III clinical trials, but they were never compared. We decided to conduct a systematic review of randomized controlled trials and meta-analyses. A total of 6,589 articles were found after searching PubMed, OVID Embase, OVID Medline, PubMed Central, and clinicaltrials.gov. Only full-text peer-reviewed articles published in the past six years were put through the Cochrane bias assessment tool or the Assessment of Multiple Systematic Reviews (AMSTAR) tool to screen for bias. After strict quality assessment, data from five randomized controlled trials (n=2,694) and three systematic reviews/meta-analysis (n=8,898) was extracted and included. The data extraction from these studies showed that semaglutide and OCA cause histological improvement, but NASH resolution is exclusive to semaglutide. Although high doses of OCA can cause dyslipidemia and severe pruritus, it is the only therapeutic that causes improvement in NASH-associated hepatic fibrosis. Semaglutide is the safest option among the two and leads to significant weight loss compared to OCA; thus, a better outcome on hepatic steatosis follows. The indications of each of these drugs should be based on the NAFLD activity score and NASH fibrosis stage. OCA should be used with caution among patients with hyperlipidemia and ischemic heart disease as it may make these conditions worst.
Efficacy and safety of oral semaglutide in patients with non-alcoholic fatty liver disease complicated by type 2 diabetes mellitus: A pilot study. [2022]This study aimed to clarify the efficacy and safety of oral semaglutide treatment in patients with non-alcoholic fatty liver disease (NAFLD) complicated by type 2 diabetes mellitus (T2DM).
Effect of semaglutide on fatty liver disease biomarkers in patients with diabetes and obesity. [2023]This work aims to assess the effect of weekly subcutaneous semaglutide on biomarkers of metabolic-associated fatty liver disease (MAFLD), namely the hepatic steatosis index (HSI) and the fibrosis-4 (FIB-4) index, at 24 weeks in outpatients attended to in internal medicine departments.
Comparative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitor and 4 glucagon-like peptide-1 (GLP-1) receptor agonist drugs in non-alcoholic fatty liver disease: A GRADE-assessed systematic review and network meta-analysis of randomized controlled trials. [2023]Background: The relative efficacy of 5 sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and 4 glucagon-like peptide-1 (GLP-1) receptor agonists for non-alcoholic fatty liver disease (NAFLD) therapy has not been sufficiently investigated. Methods: Randomized controlled trials (RCTs) in which patients with NAFLD were treated with SGLT-2 inhibitors or GLP-1 receptor agonists were included. Primary outcomes were improvements in liver enzymes and liver fat parameters, while secondary outcomes included anthropometric measures, blood lipids and glycemic parameters. The frequentist method was used to perform a network meta-analysis. Evidence certainty was assessed using the grading of recommendations assessment, development, and evaluation (GRADE). Results: The criteria were satisfied by 37 RCTs with 9 interventions (5 SGLT-2 inhibitors and 4 GLP-1 receptor agonists). Based on high certainty evidence, in patients with NAFLD (or comorbid with type 2 diabetes), semaglutide could lower alanine aminotransferase as well as aspartate aminotransferase, γ-glutamyl transferase, controlled attenuation parameter, liver stiffness measurement, body weight, systolic blood pressure, triglycerides, high-density lipoprotein-cholesterol, glycosylated hemoglobin. Liraglutide could lower alanine aminotransferase as well as subcutaneous adipose tissue, body mass index, fasting blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment, while dapagliflozin could lower alanine aminotransferase as well as body weight, fasting blood glucose, postprandial blood glucose, glycosylated hemoglobin, glucose and homeostasis model assessment. Conclusion: Semaglutide, liraglutide, and dapagliflozin all have a certain effect on NAFLD (or comorbid with type 2 diabetes) based on high confidence evidence from indirect comparisons, and semaglutide appears to have a therapeutic advantage over the other included medicines. Head-to-head studies are needed to provide more confidence in clinical decision-making.