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GLP-1 RAs may reduce opioid overdose risk by 40%

People with opioid or alcohol use disorder (OUD, AUD) who take glucagon-like peptide-1 receptor agonists (GLP-1 RAs) to treat diabetic/weight-related conditions appear to have a 40% lower rate of opioid overdose and a 50% lower rate of alcohol intoxication than people with OUD and AUD who do not take the medications, according to researchers from Parkinson School of Health Sciences and Public Health, Loyola University Chicago, Maywood, IL.


GLP-1 RAs medications are known to interact with the mesolimbic system region of the brain to reduce appetite and trigger satisfaction after eating. The mesolimbic system overlaps with the brain processes that govern addictive behaviours. This overlap suggests that GLP-1 RAs and similar medications might also alter the reward-response pathways associated with substance use.


“Prescriptions of glucose-dependent insulinotropic polypeptide and/or glucagon-like peptide-1 receptor agonists appear to be associated with lower rates of opioid overdose and alcohol intoxication in patients with opioid use disorder and alcohol use disorder,” the study authors noted. “The protective effects are consistent across various subgroups, including patients with comorbid type 2 diabetes and obesity.”


Until now, most of the existing research into using GLP-1 RAs and GIPs to treat substance use disorders consists of animal studies and small-scale clinical trials. This new large-scale human study looked at 503,747 people with a history of OUD, of which 8,103 had a prescription for a GLP-1 RA or GIP. The study found that people with OUD who had a GLP-1 RA or GIP prescription had a 40% lower rate of opioid overdose compared with those who did not have a prescription.


The study also looked at 817,309 people with a history of AUD, of which 5,621 had a prescription for a GLP-1 RA or GIP. The study found that people with AUD who had a GLP-1 RA or GIP prescription had a 50% lower rate of alcohol intoxication compared with those who did not have a prescription.


Patients with GIP/GLP-1 RA prescriptions demonstrated statistically significantly lower rates of opioid overdose [adjusted incidence rate ratio (aIRR) in OUD patients: 0.60; 95% confidence interval (CI) = 0.43–0.83] and alcohol intoxication (aIRR in AUD patients: 0.50; 95% CI = 0.40–0.63), compared to those without such prescriptions. When stratified by comorbid conditions, the rate of incident opioid overdose and alcohol intoxication remained similarly protective for those prescribed GIP/GLP-1 RA among patients with OUD and AUD.


“Our study, focusing on assessing the association between GIP/GLP-1 RA prescriptions and substance-related outcomes, specifically opioid overdose and alcohol intoxication, in patients with OUD and AUD, reveals the possibilities of a novel therapeutic pathway in substance use treatment. The potential of GIP/GLP-1 RA medications, traditionally used for metabolic disorders, in mitigating these critical substance-related outcomes emphasizes the importance of exploring existing drugs for new applications. Although the results are promising, they highlight the need for further research, particularly prospective clinical trials, to validate these associations and understand the underlying mechanisms,” they study’s authors concluded. “This study not only contributes to the evolving landscape of substance use therapy but also opens avenues for more comprehensive and effective treatment strategies for those affected by OUD and AUD.


The findings were featured in the paper, ‘The association between glucose‐dependent insulinotropic polypeptide and/or glucagon‐like peptide‐1 receptor agonist prescriptions and substance‐related outcomes in patients with opioid and alcohol use disorders: A real‐world data analysis’, published in the journal Addiction ( a journal from the Society for the Study of Addiction).

To access this paper, please click here

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