GLP-1 Drugs Could Help People With Alcohol Use Disorder

Some GLP-1 receptor agonists may hold promise as treatments for alcohol use disorder (AUD), a Swedish observational study suggested.

Among more than 200,000 individuals with AUD, those taking semaglutide (Ozempic, Wegovy) had a 36% reduced risk for AUD-related hospitalization compared with those not taking a GLP-1 agent (adjusted hazard ratio [aHR] 0.64, 95% CI 0.50-0.83), Markku Lähteenvuo, MD, PhD, of the University of Eastern Finland in Kuopio, and colleagues reported.

The GLP-1 agonist liraglutide (Victoza, Saxenda) was also linked with a significantly reduced risk of AUD hospitalization (aHR 0.72, 95% CI 0.57-0.92), they wrote in JAMA Psychiatry.

Dubbed an “especially interesting” finding, the researchers said these two agents actually had better risk reduction than AUD medications including naltrexone, disulfiram, and acamprosate. Use of these AUD medications was only associated with a “modestly decreased risk” of hospitalization (aHR 0.98, 95% CI 0.96-1.00).

However, this comparison “needs to be taken with a grain of salt,” they said, adding that “the comparators were different: GLP-1 agonist use was compared with the times GLP-1 agonists were not used, and AUD medication use compared with times when AUD medications were not used.”

Both semaglutide and liraglutide are approved to treat type 2 diabetes and obesity or overweight, but a wave of recent research has looked into potential clinical benefits of GLP-1 drugs beyond these indications. Some data have indicated promise for lowering the risk of Alzheimer’s disease and glaucoma in certain patients, as well as utility in several addiction-related disorders like opioid use disorder and tobacco use disorder.

“As the GLP-1 receptor [semaglutide] has been shown to be involved in many pathways related to craving and reward, it may be plausible that GLP-1 agonists could be used for a wide variety of addictions,” Lähteenvuo’s group noted.

“In humans, genetic variation in GLP-1R has been shown to be associated with increased risk of AUD,” they added. “A recent review suggested that GLP-1 agonists may exert a centrally mediated effect to reduce addictive behavior at least partly via dopamine modulation.”

Utilizing real-world data, the researchers looked at Swedish individuals identified from registries of inpatient care, specialized outpatient care, sickness absence, and disability pension from January 2006 to December 2023; 63.5% of the included cohort were male and the average age was 40.

During the median 8.8-year follow-up, 58.5% of the 227,866 individuals with AUD experienced an AUD-related hospitalization. Of these, 6,276 were GLP-1 agonist users, with most on semaglutide (n=4,321), followed by liraglutide (n=2,509), dulaglutide (Trulicity; n=1,118), and exenatide (Byetta, Bydureon; n=98). By the end of follow-up, half of GLP-1 agonist users had cardiovascular disease, 43.7% had type 2 diabetes, 18.7% had obesity, and 10.7% had kidney disease.

Beyond AUD-specific hospitalizations, semaglutide users also had a 32% reduced risk for any substance use disorder-related hospitalization than nonusers (aHR 0.68, 95% CI 0.54-0.85). Liraglutide was also associated with a significantly reduced risk of substance use disorder-related hospitalizations, albeit to a slightly lesser extent (aHR 0.78, 95% CI 0.64-0.97).

But Lähteenvuo’s group said this result “needs to be interpreted cautiously, as the majority of these hospitalizations were from alcohol-related causes.”

Dulaglutide was not linked with a lower risk of AUD-related or substance use disorder-related hospitalization, nor was exenatide associated with a lower risk of substance use disorder-related hospitalization.

The researchers also looked into hospitalizations for somatic reasons. Again, semaglutide was associated with the lowest risk (aHR 0.78, 95% CI 0.68-0.90), liraglutide with the second lowest risk (aHR 0.79, 95% CI 0.69-0.91), and AUD medications with the third lowest risk (aHR 0.85, 95% CI 0.83-0.88).

Of note, GLP-1 agents were not tied with an increased risk for suicide attempt, but AUD medications were associated with a slightly increased risk for suicide attempt (aHR 1.15, 95% CI 1.08-1.22). Evidence has been mixed on whether there is an association between GLP-1 drugs and suicidal thoughts, but recent data has suggested otherwise.

While the observational nature of the current study prohibits any causal inferences, the researchers said the next step should include randomized clinical trials to formally test GLP-1 agonists as potential AUD and substance use disorder treatments.

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