Non-Alcoholic Fatty Liver Disease, the HEpatic Response to Oral Glucose, and the Effect of Semaglutide (NAFLD HEROES)

What Was Tested

In this phase 2 trial, researchers set out to test Semaglutide for fatty liver & elevated liver enzymes.

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.

It had three arms (groups): Arm A: Steatosis (experimental), Arm B: NASH (experimental) and Arm C: Healthy (no intervention).

Participants with steatosis on baseline biopsy.

Participants with NASH on baseline biopsy.

Healthy Volunteers.

The registry classes the interventions as drug.

More on the Plan

Despite recent advances, there is still a considerable knowledge gap regarding the fundamental pathogenic mechanisms, and especially regarding the transition from benign steatosis to steatohepatitis.

Although NAFLD reflects disordered energy metabolism in the liver, little information exists on the response of the human liver to the acute caloric load of a meal.

The researchers further hypothesize a spillover effect, wherein NASH patients have an impairment of the hepatic ability to esterify the load of FA to triglycerides (TG) compared to patients with steatosis, resulting in accumulation of lipotoxic intermediary metabolites.

Their aims in this study are (1) to assess the hepatic response to an acute oral carbohydrate load; (2) to identify which baseline parameters can predict the clinical response of NAFLD patients to a course of semaglutide, a novel GLP-1RA.

Who Took Part

Enrollment: 104 planned participants were the target.

It was open to people of any sex aged from 18 years up to 100 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Male or female Aged \>= 18 years of age. Ability of subject to understand and the willingness to sign a written informed consent document. Presence of NAFLD (steatosis grade greater than or equal to 1 on NASH-CRN scoring scale) on baseline admission liver biopsy.

The full record lists 7 inclusion and 44 exclusion criteria; among the exclusions: pregnant or breast-feeding; HIV infection; concomitant liver disease such as autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, wilson s disease, alpha-1 antitrypsin deficiency, hereditary hemochromatosis.

How the Study Was Run

Design: non-randomized, parallel-group and open-label.

The Semaglutide group and the comparison group ran side by side rather than switching.

Everyone knew when Semaglutide was being given (open label), which is simpler to run but leaves more room for expectations to affect what is reported.

It started in 2019-07-24 with completion listed for 2027-09-03.

It ran at 1 site in United States.

Its stated primary purpose is basic science.

What Was Measured

The main thing measured (primary outcome): Change in hepatic gene expression.

What This Means in Plain Language

Put simply, this is a phase 2, non-randomized trial of Semaglutide in 104 people with fatty liver & elevated liver enzymes.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Semaglutide compound page, Fatty liver & elevated liver enzymes research.