GLP-1 Agonist Anti-Obesity Meds Reduced Alcohol Use Disorder-Related Hospitalizations

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The glucagon-like peptide-1 receptor (GLP-1) agonists, semaglutide and liraglutide, were associated with a decreased risk of hospitalization for alcohol use disorder (AUD), in an observational cohort study of patients with alcohol or substance use disorders (SUD) who were receiving the agents for obesity or type 2 diabetes.¹

"AUDs and SUDs are undertreated pharmacologically, despite the availability of effective treatment.However, novel treatments are also needed because existing treatments may not be suitable for all patients," observed Markku Lähteenvuo, MD, PhD, Department of Forensic Psychiatry, Niuvanniemi Hospital, University of Eastern Finland, Niuvankuja, Finland, and colleagues.

The possibility that GLP-1 agonist antiobesity agents might aid in reducing alcohol consumption and benefit those with AUD has been suggested in preclinical and initial human studies.

A posited mechanism was described in a statement² from the National Institute on Alcohol Abuse and Alcoholism (NIAAA), released on the publication of a study³ showing semaglutide reduced alcohol consumption and binge-like drinking in a rodent model of alcohol misuse.

"Parts of the brain that drive eating behaviors overlap extensively with the drive to use alcohol or other substances," explained Lorenzo Leggio, MD, PhD, and Leandro Vendruscolo, PharmD, PhD, of the NIAAA and the National Institute on Drug Abuse (NIDA).

The finding that semaglutide suppressed alcohol intake in different animal models of alcohol misuse "provides compelling support for testing semaglutide in future clinical trials in people with AUD," according to Leggio and colleagues. However, they caution in this and other commentary,³ that GLP-1 agonists should not be used in treating AUD until efficacy and safety are demonstrated in clinical trials.

Lähteenvuo and colleagues agree, and so qualified the findings from the cohort study.They characterize the study as an analysis of real word data on the potential of GLP-1 agonists as a treatment for reducing alcohol-related harms, but emphasize that randomized clinical trials are "urgently needed to confirm whether GLP-1 agonists could be used to treat AUD and SUDs."

"Within Individual"-Control Constrains Comparisons

The investigators used Swedish nationwide electronic registries to identify 227,868 individuals with an AUD, of whom 6276 had also been treated with a GLP-1 agonist. In addition to capturing exposure to the GLP-1 agonists exenatide, liraglutide, dulaglutide, and semaglutide, their analysis accounted for use of AUD medications, disulfiram, acamprosate, and naltrexone.

The study used a within-individual design, wherein each individual acts as their own control in calculating within-individual risk of outcome associated with periods of use vs nonuse of the pharmacotherapies. The main outcome measure was hospitalization due to AUD; with secondary outcomes of hospitalization due to SUD or to somatic reasons.Analysis compared the outcomes with use or nonuse of GLP-1 agonists, as well as nonuse with use of specific AUD medications. The cohort was followed for a median of 8.8 (4.0-13.3) years.

A total of 133,210 individuals were hospitalized because of AUD, and 138,390 because of any SUD at least once during the study period. Lähteenvuo and colleagues reported that use of semaglutide was associated with the lowest risk (AUD: aHR, 0.64 [95% CI, 0.50-0.83]; SUD: aHR, 0.68 [0.54-0.85]) and liraglutide with second lowest risk of both AUD and SUD-related hospitalizations. Neither exentatide or dualglutide were associated with statistically significant reduced risk of AUD or SUD-related hospitalization.

The reduction in AUD-related hospitalizations associated with GLP-1 agents was greater than with any of the AUD medications, but the investigators caution that the difference should be taken with a grain of salt, as the comparators were different.

"We didn't actually compare GLP-1s against AUD-medications, which is exactly why we caution against making interpretations on which group is actually better," Lähteenvuo explained to Psychiatric Times.

"The within-individual analysis works in a way where we compare the risk of an individual to get hospitalized during times when (s)he is using vs is not using a medication. Thus, when calculating the risk times for individuals using GLP-1s (or) when not using GLP-1s, they may or may not be using AUD-medications during those time windows," he pointed out. "We do try to correct the analysis for the use of other medications, but this is done mathematically/statistically, so there is always a risk for error."

Although the use of AUD medications in general was not associated with significantly altered risk, naltrexone was associated with reduced risk (AUD: aHR, 0.86 [0.83-0.89]; SUD: aHR, 0.86 [0.84-0.90]).

"I do hope this is an actual finding, and as an addiction specialist myself, I do use naltrexone quite a lot and it does seem to help people with addictions,” Lähteenvuo commented.

"Probably this effect would be explained by naltrexone reducing alcohol use, both amount of drinking days and amounts consumed when drinking, which has been shown by previous reports," he noted. "The reduction in alcohol consumption would then likely lead to reduced risks for alcohol related somatic problems, such as pancreatitis, liver cirrhosis and gastritis, and thus reduced need for hospitalizations due to these problems."

While anticipating randomized controlled trials (RCTs), Läahteenvuo expects that the findings from the cohort study will also be useful in determining the potential of GLP-1 agonists in treating AUD.

"This is one more piece for the emerging puzzle," Lähteenvuo said. "RCTs are needed to confirm these findings and preliminary reports from the first RCTs are coming up shortly, so hopefully we'll have a better picture on whether these medications will be useful or not."

Dr Bender reports on medical innovations and advances in practice and edits presentations for news and professional education publications. He previously taught and mentored pharmacy and medical students, and he provided and managed pharmacy care and drug information services.

References

1. Lähteenvuo M, Tiihonen J, Solismaa A, et al. Repurposing semagludtide and liraglutide for alcohol use disorder. JAMA Psychiatry. 2024:e243599.

2. NIAAA. Semaglutide shows promise as a potential alcohol use disorder medication. News and Events, March 13, 2024. Accessed December 23, 2024. https://www.niaaa.nih.gov/news-events/research-update/semaglutide-shows-promise-potential-alcohol-use-disorder-medication

3. Leggio L, Hendershot CS, Farokhnia M, et al. GLP-receptor agonists are promising but unproven treatments for alcohol and substance use disorders. Nat Med. 2023;29(12):2993-2995.