TOPLINE

Among individuals with opioid use disorder (OUD), the initiation of GLP-1 receptor agonists (GLP-1 RAs) was not associated with an increased risk for adverse gastrointestinal, renal, respiratory, or psychiatric outcomes. In addition, it was associated with lower risks for pancreatitis, insomnia, and anxiety than no initiation.

METHODOLOGY

• GLP-1 RAs are now foundational therapies for type 2 diabetes (T2D) and obesity; however, people with active substance use, including OUD, are often excluded from trials and observational studies, leaving a gap in real-world safety data for this group.
• To address this, researchers conducted a real-world retrospective cohort study that emulated a target trial using national commercial claims data to assess the safety of GLP-1 RAs among adults with OUD who had at least one qualifying indication for therapy (T2D, obesity, or overweight with an obesity‑related comorbidity).
• They matched 2669 GLP‑1 RA users aged 18-64 years who started therapy at or after diagnosis of OUD with an equal number of nonusers using propensity scores. All participants had continuous enrollment for at least 6 months before and after initiation of treatment.
• Ten prespecified safety outcomes were assessed: gastroparesis, pancreatitis, acute kidney injury, aspiration pneumonitis, and six psychiatric outcomes (anxiety, depression, stress-related disorders, eating disorders, insomnia, and suicidal behavior or ideation).
• For each outcome, a separate matched cohort was created, excluding those who had that same outcome in the previous year; these cohort sizes ranged from 1472 to 2329 pairs. Follow-up continued until the earliest occurrence of the outcome, disenrollment, or end of the study period.

TAKEAWAY

• The use of GLP-1 RAs was associated with a lower risk for pancreatitis than nonuse (adjusted hazard ratio [aHR], 0.65; 95% CI, 0.45-0.93); no increased risk was seen for gastroparesis.
• For psychiatric outcomes, GLP-1 RA use was linked to lower risks for insomnia (aHR, 0.78; 95% CI, 0.68-0.89) and anxiety (aHR, 0.76; 95% CI, 0.67-0.86) than nonuse; no increased risks were observed for depression, stress‑related disorders, eating disorders, or suicidal behavior or ideation.
• No increased risks were observed for acute kidney injury or aspiration pneumonitis with use vs nonuse of GLP-1 RAs.

IN PRACTICE

“Our study establishes a strong safety profile for GLP-1 RA use among individuals with OUD in real-world clinical settings, reinforcing their safe use for approved indications in this medically complex population. As GLP-1 RAs continue to expand in scope and cost, ensuring their safety in high-risk populations is critical. Our results support their continued use while also laying the groundwork for future repurposing trials targeting addiction outcomes,” the authors wrote.

SOURCE

The study was led by Tahmid Hussain, University of Florida, Gainesville. It was published online in Diabetes, Obesity and Metabolism.

LIMITATIONS

Because the study was observational, residual or unmeasured confounding could not be ruled out. Changes in health status during the follow‑up period may have influenced the results. Complete information on key clinical factors that may have affected both treatment initiation and outcomes was unavailable in the claims data, and medication exposure may have been misclassified.

DISCLOSURES

No funding source was reported for the study, and the authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.