Recent research published in JAMA Psychiatry We found 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 drugs were originally developed to treat type 2 diabetes and obesity, and were associated with a reduced risk of hospitalization for alcohol use disorder in people who also had obesity and diabetes. Surprisingly, the risk reduction was greater than that observed with officially approved treatments for alcohol use disorder, highlighting the need for further research to confirm these findings. I am.
Alcohol use disorder is a chronic disease characterized by an inability to control alcohol intake, even though it negatively impacts health, relationships, and daily life. This is a complex disease that is 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 problems, accidents, and a variety of chronic diseases. Treatment usually involves a combination of psychosocial therapies, such as counseling and support groups, and pharmacological interventions. Drugs such as naltrexone, disulfiram, and acamprosate are approved to treat alcohol use disorder, but they are often underprescribed and do not work for everyone, making effective treatment difficult. There remains a wide gap in options.
GLP-1 agonists, on the other hand, are drugs originally developed to manage 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 metabolic benefits, research suggests that GLP-1 agonists may affect the brain’s reward pathways, which play a central role in addictive behaviors. Preclinical studies in animals and anecdotal observations in humans suggest that it has the ability to reduce alcohol craving and drinking.
“I work as an addiction specialist, and I have heard from both patients and colleagues that people being treated with GLP-1 agonists (particularly semaglutide) have no interest in using alcohol for any reason. We started receiving feedback that it seemed like we were losing it (and some people were disgusted),” said study author Marku Rehtinvuo, a forensic psychiatry doctor at the University of Eastern Finland and Niuvanniemi Hospital.
“While there are some great medications to treat alcohol use disorder, they are not suitable or effective for everyone, so adding additional medications to your toolbox is extremely important. We thought that would be great. If this could be accomplished through repurposing (using an existing approved drug for a new indication), even better, as it is often faster than starting a development project from scratch. It will be.”
Researchers analyzed data from Sweden’s national electronic register, allowing them to study a cohort of more than 227,000 people diagnosed with alcohol use disorder between 2006 and 2021. These individuals were followed for up to 15 years, providing a robust dataset to examine the relationship between the two. Drug use and health effects.
To identify drug use, the researchers employed sophisticated methods that recreated the period during which participants were actively prescribed a particular drug. Although the primary focus was on GLP-1 agonists such as semaglutide and liraglutide, a secondary focus was placed on officially approved alcohol use disorder treatments such as naltrexone, disulfiram, and acamprosate. This study primarily investigated the risk of hospitalization for alcohol use disorder as the outcome of interest. Secondary outcomes included hospitalization for other substance use disorders, physical illness, and suicide attempts.
A unique feature of this study was the within-individual design, comparing periods of drug use and non-use within the same individual. This approach reduced the potential for confounding factors that could bias the results, such as differences in individual health status or baseline risk.
This study found that the use of semaglutide and liraglutide was associated with a lower risk of hospitalization for alcohol use disorder. Use of semaglutide was associated with a 36% reduction in risk, and use of liraglutide was associated with a 28% reduction in risk. These reductions were significantly greater than those observed with drugs approved for alcohol use disorder. For example, naltrexone, the most effective of the approved options, was associated with a 14% risk reduction.
“We were surprised that the hazard ratio for GLP-1 agonists was similar to (or even better than) that for actual alcohol use disorder drugs like naltrexone. However, when directly comparing GLP-1 agonists and naltrexone, It’s not about these drugs,” Leteenvuo told PsyPost.
Beyond alcohol use disorder, drug use also reduced the risk of hospitalization for substance use disorder and physical illness. Semaglutide reduced hospitalizations for substance use disorders by 32% and hospitalizations for physical illnesses by 22%. A similar pattern was observed with liraglutide, although the effect was slightly smaller.
Interestingly, this study did not find a statistically significant association between GLP-1 agonist use and hospitalization for suicide attempts. This finding is in contrast to the increased risk of suicide attempts observed with some approved alcohol use disorder treatments.
“Since our study is registration-based, any results should be taken with a grain of salt and we should not talk about causation,” Leteenvuo explained. “But I think our study is one of a number of studies that already seem to show that GLP-1 agonists may be useful in treating alcohol use disorder. Some There are mechanistic studies, there are animal studies, there are registry studies, and now we’re hearing that the first randomized controlled trials are also being announced, all of which suggest we may be finding something here. It seems to indicate that.”
“Thus, I think our study results should be treated as a preliminary indication that GLP-1 agonists could be used for alcohol use disorder, but this does not mean patients are prescribed these drugs. However, because these drugs have approved indications, doctors should consider one of two equally effective alternatives for diabetes. Diabetic patients who also seek support for alcohol abuse in situations where (official indication). .
“Also, we did not detect an increase in signals of suicidal behavior,” Leteenvuo continued. “This was a concern for GLP-1 agonists several years ago, and this is consistent with a very large study recently conducted by the European Medicines Agency.” Not found There is no evidence of any increase in suicidal behavior. ”
However, this study has important limitations. Being an observational study, it cannot establish cause and effect, only associations. Although within-individual designs can help reduce some biases, they cannot completely eliminate residual confounding. Furthermore, because this study relied on registry data, it may not capture all relevant variables, such as alcohol consumption patterns or adherence to prescribed medications.
Researchers emphasize the need for randomized clinical trials to confirm the efficacy and safety of glucagon-like peptide-1 receptor agonists in the treatment of alcohol use disorder. These trials will provide more conclusive evidence by directly comparing the drug to a placebo or approved treatment in a controlled setting.
“Because our study was a registration study, there could always be sources of bias that we were not able to detect or control,” Leteenvuo noted. “Although we have performed a significant number of additional analyzes to do our best to remove bias, there is always the possibility that some will remain. That is why other groups may develop their own cohorts or randomized controlled trials. It is always important to confirm our findings with.” Also, register studies cannot speak of causation, only of association, as mentioned above. ”
“Our research group (led by Professor Jari Tihonen) has been doing medical epidemiology for decades. We want to continue this direction and only look at the comparative effectiveness of approved medicines. We hope to use the registry data to make interesting discoveries, as well as explore possibilities for reuse, such as in this study.”
“We cannot emphasize enough that based on our results alone, GLP-1 agonists should not be prescribed for alcohol use disorder,” added Leteenvuo. “Randomized controlled trials are still needed for confirmation.”
the study, “Repurposing semaglutide and liraglutide for alcohol use disorder” authors are Markku Lähteenvuo, Jari Tiihonen, Anssi Solismaa, Antti Tanskanen, Ellenor Mittendorfer-Rutz, and Heidi Taipale.
