GLP-1s Linked to Lower Substance Use Disorder Risk in Veterans With Diabetes

New research suggests a potential benefit of GLP-1 receptor agonists – medications initially developed for type 2 diabetes – in reducing the risk of substance leverage disorders. A study published in The BMJ found that veterans with type 2 diabetes treated with GLP-1s had a lower incidence of both developing new substance use disorders and experiencing adverse outcomes related to pre-existing addictions, compared to those treated with SGLT-2 inhibitors. This adds to a growing body of evidence hinting at broader anti-addictive properties of these medications, potentially offering a novel approach to tackling a complex public health challenge.

GLP-1s and Reduced Substance Use Risk in Veterans

The research, led by Ziyad Al-Aly, MD, FASN, chief of research and development at Veterans Affairs St. Louis Health Care System, analyzed data from over 606,000 U.S. Veterans with type 2 diabetes. The study employed an emulated parallel, new user, active comparator target trial design, comparing outcomes between those prescribed GLP-1 receptor agonists and those receiving SGLT-2 inhibitors. Researchers followed participants for three years, tracking diagnoses of substance use disorders involving alcohol, cannabis, cocaine, nicotine, and opioids, as well as other less common substances.

The findings revealed a consistent pattern: veterans taking GLP-1s demonstrated a reduced risk for developing substance use disorders across the board. Specifically, the hazard ratios (HR) were as follows: alcohol (HR = 0.82), cannabis (HR = 0.86), cocaine (HR = 0.8), nicotine (HR = 0.8), opioids (HR = 0.75), and a composite of all SUDs (HR = 0.86). These results suggest a potential protective effect of GLP-1s against a wide range of addictive behaviors. Previous research has also explored the potential benefits of GLP-1s on brain health, including impacts on addiction, depression, and cognition.

Benefits for Those with Existing Substance Use Disorders

Importantly, the study also examined the impact of GLP-1s on individuals already diagnosed with a substance use disorder. The results were encouraging. Compared to those taking SGLT-2 inhibitors, veterans on GLP-1s experienced a significantly lower risk of adverse clinical outcomes, including emergency department visits (HR = 0.69), hospital admissions (HR = 0.74), mortality (HR = 0.5), and drug overdose (HR = 0.61). The risk of suicidal ideation or attempts was also reduced (HR = 0.75). This suggests that GLP-1s may not only prevent the development of new addictions but also help mitigate the harms associated with existing ones.

“There is no approved medication for cocaine or methamphetamine addiction, and fewer than 2% of people with alcohol use disorder receive any medication at all,” Al-Aly said. “The treatment gap is enormous. These findings offer the most promising signal for new addiction treatments in decades.”

How Might GLP-1s Impact Addiction?

The precise mechanisms underlying these observed effects remain under investigation. GLP-1s work by mimicking the action of glucagon-like peptide-1, a natural hormone that regulates blood sugar levels. However, GLP-1 receptors are also found in the brain, particularly in areas involved in reward and motivation. Dr. Al-Aly has suggested that GLP-1s may exert their anti-addictive effects by modulating these brain pathways, reducing cravings and impulsivity. The breadth of impact across multiple substances is particularly noteworthy, as most existing addiction medications target specific substances.

Study Limitations and Considerations

While the findings are promising, it’s crucial to acknowledge the study’s limitations. The research population consisted primarily of older, white male veterans, which limits the generalizability of the results to other populations. The study relied on electronic health records, which may be subject to inaccuracies or misclassifications. The observational nature of the study means that it cannot definitively prove a causal relationship between GLP-1 use and reduced substance use risk. Confounding factors, such as socioeconomic status, were difficult to fully account for.

It’s also important to note that the study did not assess the impact of GLP-1s on the severity of addiction or the duration of abstinence. Further research is needed to determine the optimal dosage, duration of treatment, and long-term effects of GLP-1s in the context of substance use disorders.

What’s Next for GLP-1 Research and Addiction Treatment?

The researchers emphasize the urgent need for randomized controlled trials to confirm these findings and explore the potential of GLP-1s as a novel addiction treatment. These trials should include diverse populations, including individuals without diabetes, and should focus on clinically meaningful outcomes, such as overdose rates, hospitalizations, and mortality. Current global events highlight the importance of addressing mental health and addiction vulnerabilities.

In the meantime, clinicians may consider these findings when making treatment decisions for patients with type 2 diabetes and a history of substance use. As Dr. Al-Aly suggests, choosing a GLP-1 drug over other options may offer additional benefits for these individuals. However, it’s essential to emphasize that GLP-1s are not a standalone solution for addiction and should be used in conjunction with other evidence-based treatments, such as counseling and behavioral therapy. The U.S. Department of State offers resources for Americans abroad who may be struggling with substance use, including access to support and treatment options: https://mytravel.state.gov/s/crisis-intake.

The potential for GLP-1s to address the addiction crisis represents a significant step forward, but further research and careful clinical implementation are essential to realize its full potential. Ongoing surveillance and monitoring of real-world outcomes will also be crucial to assess the long-term safety and effectiveness of these medications in the context of substance use disorders.