Glucagon-like peptide-1 (GLP-1) receptor agonists are a type of medication used to treat type 2 diabetes mellitus and obesity. [1] They are often referred to as the ‘weight loss jab’, with examples including semaglutide (Wegovy) and liraglutide (Saxenda). [1] Research has also shown their potential in substance use treatment, with GLP-1s associated with a 39% lower repeat-overdose risk. [2] However, it’s important to note that this is an association, rather than confirmation that GLP-1 use always lowers repeat-overdose risk. [2]
A new study on GLP-1 and repeat overdose risk
Adults who overdose on alcohol or illicit substances are at a higher risk of repeated future overdoses. [2] This analysis, conducted by Epic Research using de-identified electronic health records from more than 300 million patients, aimed to determine whether GLP-1 use affects repeat-overdose risk. Two research teams worked independently and reached similar conclusions, though the analysis has not been published in a peer-reviewed journal. [2]
The data were gathered from adults in the U.S. attending a hospital between January 2017 and March 2026 due to an overdose. [2] These individuals were then followed up to establish whether there was any repeat overdose and whether they were prescribed a GLP-1. [2]
The study followed up on more than 680,000 adults after an overdose
Approximately 683,800 individuals were identified and followed up during this study. [2] This included individuals with a range of ages, incomes, and backgrounds, as well as different substances used.[2]
- Individuals who had previously been prescribed a GLP-1 before the overdose were excluded from the study.[2]
- To be included, patients also needed a BMI of 25 or higher and a history of regular contact with the healthcare system: at least one outpatient visit more than a year before the overdose and one after.
- Assault-related and methadone overdoses were excluded.
- The BMI requirement matters when interpreting the results: this was a group already likely to be considered for GLP-1 prescribing on weight grounds, not overdose survivors in general. [2]
To check whether the finding held up, the researchers repeated their analysis on three separate patient subgroups: those whose first overdose involved alcohol, those whose first overdose did not involve alcohol, and individuals not receiving any addiction-treatment medications. [2]
Active GLP-1 use associated with a 39% lower repeat-overdose risk
The study found that after an overdose, active GLP-1 use was associated with an overall 39% lower repeat-overdose risk within three years of the initial overdose. [2] Individuals who were prescribed a GLP-1 that was later discontinued still had a 20% lower risk of repeat overdose, highlighting the potential long-term benefit of GLP-1 use. [2] The figures were similar between the subgroups, with a 40% lower risk when the overdose involved alcohol, compared to 37% when alcohol was not involved. [2] Below is a summary table containing the key findings: [2]
| Repeat overdose risk with active GLP-1 use | Repeat overdose risk with discontinued GLP-1 | |
|---|---|---|
| Overall | 39% lower | 20% lower |
| Initial overdose involving alcohol | 40% lower | 18% lower |
| Initial overdose not involving alcohol | 37% lower | 24% lower |
| No addiction treatment medications | 44% lower | 28% lower |
How GLP-1 drugs may affect substance use and overdose risk
GLP-1 medications could affect substance use outcomes as they target the same reward centers in the brain, affecting dopamine release in these areas. [3] In their traditional use, GLP-1s reduce food cravings and, in turn, reduce intake of palatable foods, making them effective in treating diabetes and obesity. [3]
This process could also be used to help reduce substance use, as continued substance use is driven by the same reward pathways in the brain. Recent studies have associated GLP-1 use with reduced alcohol intake, reduced opioid-seeking behavior, and reduced self-administration of opioid drugs.[4][5]
They have also been associated with reduced intake of cocaine, amphetamines, alcohol, and nicotine in animal studies. [3] Further large-scale research studies are required to further assess the impact of GLP-1 use for substance use disorders.
Limitations of the GLP-1 repeat overdose study
Despite the promising data in this study, there are several limitations. The key limitations are listed below: [2]
- The study notes that it found an association between GLP-1 use and reduced repeat-overdose risk, not causation.
- It acknowledges that those prescribed GLP-1s are more likely to remain engaged with healthcare professionals and have better access to care. This could represent the reason why their repeat-overdose risk is lower, rather than the GLP-1 drug itself.
- There are several unmeasured confounding factors, including the severity of substance use disorder, social support, employment, and motivation to quit.
- The reason for the GLP-1 prescription is not specified, nor is the dosing schedule.
- The reason for the GLP-1 being discontinued in certain individuals is also not specified.
- The data rely on overdoses that are treated in hospital. Therefore, this study was unable to account for overdoses that did not result in a hospital visit, either because they were managed in the community or because they led to fatality.
- GLP-1 prescriptions filled outside the contributing health systems may not have been captured in the data.
- The findings apply to patients treated within health systems contributing to this dataset, and may not generalize to the broader population.
Could GLP treatment replace overdose care and prevention?
While GLP-1s may play more of a role in the future, the essential overdose care remains the same. This includes providing and administering naloxone, emergency services treatment, inpatient care, and ongoing mental health support. [6] GLP-1s should be seen as a potential future add-on to existing care, not a substitute.
What the study could mean for future overdose prevention
If future research confirms these findings, GLP-1 medications could become a valuable tool in the effort to reduce repeat overdoses. Currently, medication treatment is specific to each substance, whereas the broad mechanism of GLP-1s could allow them to be used for a range of different substances. [2] Because GLP-1s are already FDA-approved for type 2 diabetes mellitus and obesity, they could offer clinicians a familiar, accessible treatment option.
However, it’s important to stress that further research is needed before GLP-1s could be considered as part of future overdose prevention. Researchers are likely to prioritize randomized controlled trials next, to establish whether GLP-1s directly reduce overdose risk or whether the association reflects other factors, such as healthcare engagement. [2] Trials could also help determine which patients are most likely to benefit and what dose and duration are needed.
Final thoughts
This large study adds to a growing body of evidence suggesting that GLP-1 medications may have a role to play in reducing the risk of repeated overdose.[2] This is linked to the GLP-1s’ effect on the brain’s reward system, which drives continued substance use. However, larger, controlled trials will be needed before GLP-1s can be recommended as a standard part of post-overdose care.
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