SUN-636 - Association Between GLP-1 Receptor Agonist Therapy and Incident Impulse Control Disorders in Patients With Type 2 Diabetes: A Large Propensity-Matched Cohort Study

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have expanded the treatment of type-2 diabetes mellitus (T2D) and obesity. They demonstrate metabolic and cardiovascular benefits, but how these drugs affect neuropsychiatric disorders is less well understood. Prior studies found that GLP-1RAs alleviate multiple symptoms associated with alcohol use disorder (AUD) in humans and animal models. Due to their potential effectiveness in modulating AUD, we and others have hypothesized that GLP-1RAs may have similar effects in impulse control disorders (ICD).

Methods: A retrospective cohort study was conducted using the TriNetX Global Collaborative Network. 772,943 adults with T2D receiving GLP-1RAs were compared with 772,965 patients without GLP-1RA therapy. Propensity scoring with 1:1 matching was performed for demographic factors, cardiovascular comorbidities, substance use, psychiatric medication exposure, and glycemic control. The primary outcome was incident ICD (ICD-10 F63). Secondary outcome included pathological gambling (ICD-10 F63.0). Two-sample t-test, Kaplan–Meier survival analyses, and Cox proportional hazards analyses were performed.

Results: ICDs occurred in 242 GLP-1RA users and 108 non-users. GLP-1RAs were associated with increased risk of ICDs (risk ratio = 2.241, 95% CI 1.786-2.811; hazard ratio = 2.625, 95% CI 2.088-3.300, p< 0.001). Pathological gambling was more frequent in GLP-1RA users (28 vs 12 cases; risk ratio=2.333, 95% CI 1.187-4.589). For both outcomes, the GLP-1RA cohort had a higher cumulative incidence, but the absolute risk was low.

Conclusions: Within this sample of patients with T2D, GLP-1RA therapy was associated with a small but statistically significant increase in incident ICDs and pathological gambling behavior. Although the absolute risk of these disorders remained low, our findings suggest a potential separate GLP-1 signaling pathway involved in impulsivity that warrants further investigation.

Keywords:
GLP-1 receptor agonists; impulse control disorder; pathological gambling; type 2 diabetes; pharmacoepidemiology; propensity score matching

Conflicts of interest:
All authors declare no conflicts of interest.

Acknowledgments:
Artificial intelligence tools, including ChatGPT (OpenAI), were used to prepare this abstract for tasks such as language refinement, organization of author-drafted content, and formatting assistance. All data analysis, interpretation, and critical content were conducted and reviewed by the authors. The final abstract was thoroughly edited and approved by all authors to ensure accuracy, originality, and ethical compliance.

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