Semaglutide and liraglutide linked to lower alcohol-related hospitalization risk

A recent study published in JAMA Psychiatry has uncovered promising evidence suggesting that glucagon-like peptide-1 (GLP-1) receptor agonists, particularly semaglutide and liraglutide, may be effective treatments for alcohol use disorder. These medications, originally developed to treat type 2 diabetes and obesity, were associated with reduced risks of hospitalization due to alcohol use disorder among individuals who also had comorbid obesity or diabetes. Strikingly, the reduction in risk was greater than that observed with officially approved medications for alcohol use disorder, highlighting the need for further research to confirm these findings.

Alcohol use disorder is a chronic condition characterized by the inability to control alcohol consumption despite negative consequences on one’s health, relationships, and daily life. It is a complex disorder influenced by genetic, psychological, and environmental factors.

Globally, alcohol use disorder is a leading cause of disability and death, contributing to liver disease, mental health issues, accidents, and various chronic conditions. Treatment typically involves a combination of psychosocial therapies, such as counseling or support groups, and pharmacological interventions. While medications like naltrexone, disulfiram, and acamprosate are approved for treating alcohol use disorder, they are often underprescribed and may not work for everyone, leaving a significant gap in effective treatment options.

GLP-1 agonists, on the other hand, are medications originally developed for managing type 2 diabetes and obesity. These drugs mimic the effects of a hormone called glucagon-like peptide-1, which regulates blood sugar levels and appetite. In addition to their metabolic benefits, research has suggested that GLP-1 agonists may influence the brain’s reward pathways, which play a central role in addictive behaviors. Preclinical studies in animals and anecdotal human observations have hinted at their ability to reduce alcohol cravings and consumption.

“I’ve been working as an addiction specialist and started to get feedback both from patients and colleagues that for some reason individuals treated with GLP-1 agonists (especially semaglutide) seem to lose interest in using alcohol (some even develop an aversion),” said study author Markku Lähteenvuo, a docent in forensic psychiatry at the University of Eastern Finland and the Niuvanniemi Hospital.

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“We have some great medications to treat alcohol use disorder, but they are not suitable or effective for every individual, so we thought it would be really great to get additional medication to the toolbox. If this could be attained by repurposing (using existing approved medications for new indications, it would be even better, as this is often faster than starting a development project from scratch.”

The researchers analyzed data from nationwide Swedish electronic registries, which allowed them to study a cohort of over 227,000 individuals diagnosed with alcohol use disorder between 2006 and 2021. These individuals were followed for up to 15 years, providing a robust dataset for examining the relationship between medication use and health outcomes.

To identify medication use, the researchers employed a sophisticated method to reconstruct periods when participants were actively prescribed certain drugs. The primary focus was on GLP-1 agonists, including semaglutide and liraglutide, while a secondary focus was placed on officially approved alcohol use disorder medications, such as naltrexone, disulfiram, and acamprosate. The study primarily examined the risk of hospitalization due to alcohol use disorder as the outcome of interest. Secondary outcomes included hospitalization for other substance use disorders, physical illnesses, and suicide attempts.

A unique feature of the study was its within-individual design, which compared periods of medication use to periods of non-use within the same individuals. This approach reduced the potential for confounding factors that could bias the results, such as differences in individual health status or baseline risk.

The study found that the use of semaglutide and liraglutide was associated with a reduced risk of hospitalization due to alcohol use disorder. Semaglutide use was linked to a 36% reduction in risk, while liraglutide was associated with a 28% reduction. These reductions were markedly greater than those observed with approved medications for alcohol use disorder. For example, naltrexone, the most effective among the approved options, was associated with a 14% risk reduction.

“It was a surprise that the hazard ratios for the GLP-1 agonists were on par (and even better) with those of actual alcohol use disorder medications, like naltrexone, although we didn’t do any straight head-to-head comparisons between these medications,” Lähteenvuo told PsyPost.

Beyond alcohol use disorder, the medications also reduced the risk of hospitalization for any substance use disorder and physical illnesses. Semaglutide was associated with a 32% reduction in hospitalizations for substance use disorders and a 22% reduction in hospitalizations for physical illnesses. Similar patterns were observed for liraglutide, albeit with slightly smaller effects.

Interestingly, the study did not find a statistically significant association between GLP-1 agonist use and hospitalization due to suicide attempts. This finding contrasts with the increased risk of suicide attempts observed with some approved medications for alcohol use disorder.

“Our study is register based, so any results need to be taken with a grain of salt and we shouldn’t talk about causality,” Lähteenvuo explained. “However, I think our study is another in a line of already quite a few that seem to indicate that GLP-1 agonists might be helpful in the treatment of alcohol use disorder. There are some mechanistic studies, animal studies, register studies and now I hear the first randomized controlled trial is also coming out, which all seem to indicate we might be onto something here.”

“So, I think our study results should be treated as a preliminary indication that GLP-1 agonists might be usable for alcohol use disorder, but this needs to be verified in clinical studies before patients get prescribed these medications. However, as these medications do have approved indications, maybe they could be helpful for patients with diabetes (an official indication) who are also looking for help with alcohol abuse, especially in a situation where the doctor is contemplating between two equally effective alternatives diabetes wise.

“We also didn’t detect any increased signal for suicidal behavior,” Lähteenvuo continued, “which was a concern a few years ago for GLP-1 agonists, and this is in line with the recent very large inquiry made by the European Medicines Agency, which also did not find any evidence for an increase in suicidal behavior.”

But the study has important limitations. As an observational study, it cannot establish causality, only associations. The within-individual design helps mitigate some biases, but residual confounding cannot be entirely ruled out. Additionally, the study relied on registry data, which may not capture all relevant variables, such as alcohol consumption patterns or adherence to prescribed medications.

The researchers emphasize the need for randomized clinical trials to confirm the effectiveness and safety of glucagon-like peptide-1 receptor agonists in treating alcohol use disorder. These trials would provide more definitive evidence by directly comparing the medications to placebo and approved treatments in controlled settings.

“As our study was a register study there can always remain some sources of bias that we weren’t able to detect or control for,” Lähteenvuo noted. “We did do quite a few additional analyses to do our best to remove bias, but it is always possible some may remain, which is why it is always important to have other groups confirm our findings in their own cohorts and in randomized controlled trials. Also, register studies can never speak for causality, as mentioned above, only associations.”

“Our research group (lead by Professor Jari Tiihonen) has done medical epidemiology for decades. We are hoping to continue on that line and make interesting discoveries using the registry data, both to look at comparative effectiveness of approved medications, but also to look at possible repurposing aspects, such as in this study.”

“I cannot stress enough that no one should be prescribed GLP-1 agonists for alcohol use disorder based on our results alone,” Lähteenvuo added. “We still need confirmatory randomized controlled trials.”

The study, “Repurposing Semaglutide and Liraglutide for Alcohol Use Disorder,” was authored by Markku Lähteenvuo, Jari Tiihonen, Anssi Solismaa, Antti Tanskanen, Ellenor Mittendorfer-Rutz, and Heidi Taipale.