Semaglutide for Non-alcoholic Fatty Liver Disease
(SAMARA Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of California, San Diego
Must not be taking: Weight loss medications
Disqualifiers: Excessive alcohol, Cirrhosis, Hepatitis B, others
Prior Safety Data
Approved in 6 Jurisdictions
Trial Summary
What is the purpose of this trial?Conduct a community intervention study that will 1) validate a screening approach to identify patients at risk for advanced NAFLD in the obese or T2DM population, and 2) test whether semaglutide treatment is effective for the management of significant fibrosis due to NAFLD in high-risk patients.
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 have used weight loss medications, including GLP1RA, in the last 90 days.
What data supports the effectiveness of the drug semaglutide for 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 in humans, though specific side effects and risks should be discussed with a healthcare provider.
23567How is the drug semaglutide unique in treating non-alcoholic fatty liver disease?
Semaglutide is unique because it is a glucagon-like peptide-1 (GLP-1) receptor agonist that not only improves liver health by reducing liver fat and enzymes but also promotes significant weight loss, which is beneficial for patients with non-alcoholic fatty liver disease. Unlike other treatments, semaglutide has shown exclusive effectiveness in resolving non-alcoholic steatohepatitis (NASH), a more severe form of the disease.
23468Eligibility Criteria
This trial is for adults aged 40-79 with obesity or type 2 diabetes, showing symptoms of diabetes and having a BMI ≥27 kg/m² (or ≥25 kg/m² with pre-diabetes). They must have liver fibrosis due to NAFLD but not severe cirrhosis or other chronic liver diseases. Participants should not be heavy alcohol users, on certain medications, or have had significant weight loss recently.Inclusion Criteria
My liver tests show significant scarring or stiffness.
I understand the study requirements and have signed the consent form.
My BMI is over 27, or it's over 25 and I have pre-diabetes or type 2 diabetes.
+2 more
Exclusion Criteria
Your liver stiffness is higher than 20 kilopascals.
Your kidney function is severely reduced, as measured by a specific equation.
I haven't taken any weight loss drugs, including GLP1RA, in the last 90 days.
+10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive semaglutide or placebo for the management of significant fibrosis due to NAFLD
52 weeks
Weekly visits for subcutaneous injections
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The study aims to identify at-risk individuals for advanced NAFLD and assess the effectiveness of Semaglutide in treating significant fibrosis caused by NAFLD in these high-risk patients. It compares Semaglutide against a placebo in a real-world setting.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: SemaglutideExperimental Treatment1 Intervention
2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing Semaglutide 3.0 mg/ml for subcutaneous use
Group II: PlaceboPlacebo Group1 Intervention
2.4 mg weekly for 52 weekly in a 3 ml PDS290 pen-injector containing 3.0 mg/ml of a placebo solution for subcutaneous use
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:
University of California, San DiegoLa Jolla, CA
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Who Is Running the Clinical Trial?
University of California, San DiegoLead Sponsor
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).
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 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.
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.