Semaglutide and Opioid Overdose Risk in Patients with Type 2 Diabetes and Opioid Use Disorder

Introduction

Drug overdose deaths continue to pose a significant public health challenge in the United States, with over 107,000 opioid-related fatalities in 2023. Despite the availability of medications for opioid use disorder (OUD), only a fraction of those affected receive these treatments, and many discontinue them within six months. The pressing need for alternative treatments has led to growing interest in the potential role of semaglutide, a drug primarily used for type 2 diabetes (T2D) and obesity, in reducing opioid overdose risk.

Semaglutide and Opioid Use Disorder

Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), has shown promise in modulating dopamine reward signalling, which plays a key role in addiction. Animal studies have demonstrated that GLP-1RAs can reduce the rewarding effects of drugs like heroin, and anecdotal evidence suggests semaglutide may reduce drug cravings in humans. Previous research has indicated its potential benefits for alcohol and nicotine use disorders, prompting researchers to explore its role in preventing opioid overdoses.

Study Methods

In this cohort study, data was collected from the TriNetX Analytics Platform, which provides access to deidentified electronic health records (EHRs) from more than 116 million patients in the US. The study compared semaglutide to other antidiabetic medications, such as insulin, metformin, DPP-4 inhibitors, SGLT-2 inhibitors, and other GLP-1RAs. The aim was to determine whether semaglutide could reduce the risk of opioid overdose in patients with both T2D and OUD.

Eligibility criteria included a diagnosis of both T2D and OUD, and patients had to have been prescribed semaglutide or other antidiabetic medications between December 2017 and June 2023. The study excluded patients who had undergone bariatric surgery or had conditions such as pancreatitis, thyroid cancer, or gastroparesis. The study used propensity score matching to balance patient characteristics and ensure fair comparisons between the groups.

Results

The study involved 33,006 patients, of whom 3,034 were prescribed semaglutide. After accounting for baseline differences, semaglutide users were found to have a significantly lower risk of opioid overdose compared to those on other antidiabetic medications. Hazard ratios (HRs) for overdose risk ranged from 0.32 to 0.58, depending on the comparison group, indicating a substantial reduction in overdose risk for patients taking semaglutide.

The negative control outcome, which looked at unrelated medical conditions, showed no differences between groups, adding credibility to the findings.

Discussion

These results suggest that semaglutide may have a protective effect against opioid overdoses in patients with comorbid T2D and OUD. While promising, the findings are subject to the limitations of EHR-based observational studies, including the potential for unmeasured confounding factors and biases. Further research is needed to confirm these results, particularly through randomised clinical trials.

Conclusion

Semaglutide’s potential to reduce opioid overdose risk in patients with both T2D and OUD represents a novel and exciting area of research. While further studies are necessary to validate these findings, semaglutide could offer a new therapeutic approach for preventing opioid overdoses. Its dual role in managing diabetes and potentially addressing substance use disorders could make it a valuable tool in tackling two major public health crises.

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