A potential solution for overdose risk

A new study explores the potential of diabetes drugs like GLP-1 RA and GIP agonists to reduce opioid overdoses and alcohol intoxication in patients with substance use disorders, offering hope for new treatments in the fight against addiction.

Study: 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. Image Credit: Kmpzzz / Shutterstock.com

A recent study published in Addiction examines the association between prescriptions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) and the incidence of alcohol intoxication and opioid overdose among patients with alcohol use disorder (AUD) and opioid use disorder (OUD), respectively.

Can diabetes drugs prevent opioid-related deaths?

The opioid crisis in the United States was declared a public health emergency in October 2017, with over 70,000 individuals who died to due drug overdoses that year. Following coronavirus disease 2019 (COVID-19)-related restrictions, the opioid crisis continued to worsen, with over 107,000 deaths attributed to overdoses in 2021. Despite the existence of pharmacological treatments for OUD and AUD, many people find it difficult to receive these medications due to various factors, including negative treatment stigma.

GLP-1 RA, a drug that is primarily prescribed to treat type 2 diabetes (T2D), obesity, and other weight-related conditions, stimulates insulin production and triggers satiety after eating. GLP-1 receptors are located in a region of the brain that is responsible for addictive behaviors such as chronic substance use. Therefore, GLP-1 RA and similar drugs like GIP agonists could influence the reward-response pathways linked to substance use.

About the study

The present study explores how GLP-1 RA and GIP medications affect drug and alcohol responses in a broad patient population.

The primary objective of the current study involved OUD and AUD patients to examine the strength of the association between incident opioid overdose and alcohol intoxication and GIP/GLP-1 RA prescriptions, respectively. A secondary objective was to consider patients with comorbid conditions including T2D, obesity, or both and assess the association between substance use outcomes and GIP/GLP-1 RA prescriptions.

The study cohort comprised adults with documented histories of OUD or AUD between 2014 and 2022. Patients with GIP or GLP-1 RA prescriptions were compared to those not prescribed these drugs using a retrospective cohort design.

The primary outcomes included rates of alcohol intoxication in the AUD cohort and the incidence of opioid overdose in the OUD cohort. A prescription for any GIP/GLP-1 RA medication signified exposure to the drug.

Study findings

Individuals with a GIP/GLP-1 RA prescription had an average age of about 58 years and were more likely to be female and partnered. Patients in the OUD cohort with GIP/GLP-1 RA prescriptions had a 7.1% history of opioid overdose as compared to 15.7% of those not prescribed these medications.

In the AUD cohort, of those with GIP/GLP-1RA prescriptions, 50.1% had tobacco dependence, and 15.5% had a history of mental health conditions. Among those not prescribed these medications, 34.4% had tobacco dependence, 8.8% had a history of mental health conditions, 21.8% had an alcohol intoxication history, and 14.8% had medications for alcohol use disorder (MAUD) treatment history.

Comparatively, 37.1% of individuals in the AUD cohort not prescribed GIP/GLP-1 RA medications had an alcohol intoxication history, whereas 6.2% had a history of MAUD treatment.

Patients with OUD and a GIP/GLP-1 RA prescription were associated with a 40% reduced rate of incident opioid overdose as compared to those without a prescription, regardless of the presence of comorbid conditions. Among those with T2D or obesity and a GIP/GLP-1 RA prescription, the rate of opioid overdose was 38% and 33% lower, respectively. For individuals with both T2D, obesity and a GIP/GLP-1RA prescription, the rate of opioid overdose was reduced by 35%.

Patients with AUD and a GIP/GLP-1RA prescription exhibited a 50% lower rate of incident alcohol intoxication as compared to patients not prescribed these medications. When stratified by T2D, obesity, and both conditions, the rate of incident alcohol intoxication for those with a GIP/GLP-1 RA prescription was 49%, 42%, and 42% lower, respectively, as compared to those without GIP/GLP-1 RA prescriptions.

Conclusions

The study findings indicate that GIP/GLP-1RA medications have the potential to treat substance use disorders. Although these results are promising, additional research is needed to validate and elucidate the underlying mechanisms involved in the observed associations.

The main limitation of this study is the lack of causality and its retrospective correlational nature. The data were also limited to Cerner-affiliated hospitals and clinics, which limits the generalizability of the findings.

The accuracy of the results is also subject to the limitations of electronic health records, such as real-world timing capture, greater severity in hospitals relative to the public, and differences in treatment and diagnosis across hospitals and physicians.