Novo Nordisk to test semaglutide and two other drugs in alcohol-related liver disease

Novo Nordisk plans to begin a clinical trial this month that will test semaglutide and two experimental medicines in people with alcohol-related liver disease, and the study will also measure whether participants' drinking changes ^[1]. The company says the trial is aimed at liver health, not at treating addiction ^[1].

The study, registered as NCT06409130, aims to enroll about 240 participants and is slated to begin May 20, according to a government database ^[1][2]. Its main measure is the medicines' effect on enhanced liver fibrosis, or scarring, over 28 weeks ^[1]. Novo Nordisk said secondary endpoints include safety, tolerability and changes in alcohol consumption ^[1].

"Even though not all patients in the trial will have alcohol use disorder, it is natural to include alcohol consumption as a secondary endpoint," a Novo Nordisk spokesperson said ^[1]. The spokesperson also said there is "a significant unmet medical need in alcohol-related liver disease, and the first line of treatment for the condition is lifestyle intervention to refrain from drinking alcohol" ^[1].

Three medicines will be tested alone and in combination: semaglutide, the active ingredient in Ozempic and Wegovy; cagrilintide, which mimics the hormone amylin and is being tested with semaglutide in large diabetes and weight-loss trials under the name CagriSema; and zalfermin, listed as NNC0194-0499, which acts like the metabolic hormone FGF21, produced mainly in the liver ^[1][2].

Company has ruled out addiction studies

Novo Nordisk has said since at least last year that it does not plan to study semaglutide in areas such as alcohol addiction, even as anecdotal reports and academic studies multiplied ^[1]. Chief executive Lars Fruergaard Jorgensen told CNN in August that a brain function tied to craving "is perhaps also what is benefitting some of the other addictions," but added, "You shouldn't expect that we would go in and study these addictions widely," and called the area "not the easiest to study" ^[1].

Addiction researchers welcomed the new trial. "Those of us doing work in this area see this as a step in the right direction," said Christian Hendershot of the University of North Carolina at Chapel Hill, who is running one of the few studies in the area. "Additional treatment options for this group are really needed" ^[1].

Dr. Lorenzo Leggio, a National Institutes of Health researcher, told CNN that "alcohol is now the leading cause of cirrhosis and liver transplantation in the US," and that new treatments are needed both for alcohol-associated liver disease and for the alcohol use disorder that drives it ^[1]. Leggio published a May 2023 study showing semaglutide reduced alcohol drinking in rodents ^[1].

Eli Lilly, which makes the tirzepatide drugs Mounjaro and Zepbound, said it has seen "anecdotal commentary" about GLP-1s for additional indications such as addiction but has not announced plans to develop its medicines for those uses ^[1].

Why it matters for patients

Nothing about the approved uses of semaglutide, sold as Ozempic and Wegovy, changes because of this trial. The study is not designed to answer whether these drugs help people with alcohol use disorder cut back; drinking is a secondary measure behind liver scarring ^[1]. In a December commentary in the journal Nature Medicine, Leggio, Hendershot and other researchers wrote that the drugs should not be prescribed for alcohol use disorder "until their safety and efficacy has been proven in clinical trials," adding that "well-controlled trials with scientific rigor are needed before any claim of efficacy" can be made ^[1].

Treatment options for alcohol use disorder are limited: research from the financial firm TD Cowen found fewer than 5% of the estimated 29 million Americans with the condition receive drug therapy ^[1]. About 15 million Americans are estimated to use GLP-1 medicines, according to a recent poll cited by CNN ^[1].

What happens next

The trial is slated to begin May 20, with the primary liver-scarring measure assessed over 28 weeks ^[1]. A date for results has not been disclosed. Enrollment details and eligibility criteria are listed on the trial's ClinicalTrials.gov record ^[2].