Budoor Alqinai, MBChB, MSc1, Ayowumi Adekolu, MD1, Olanrewaju Adeniran, MD2, Vibhu Chittajallu, MD3, Soban maan, MD1, Shyam Thakkar, MD1, Shailendra A. Singh, MD3 1West Virginia University, Morgantown, WV; 2West Virginia University Morgantown, Morgantown, WV; 3West Virginia University School of Medicine, Morgantown, WV Introduction: GLP-1 receptor agonists (GLP-1RAs) have revolutionized the treatment of obesity and type 2 diabetes, offering both metabolic and cardiovascular benefits. However, emerging data have raised concerns about potential neuropsychiatric effects, including mood disturbances and suicidality. While these risks have drawn increasing scrutiny, it remains unclear whether psychiatric outcomes differ based on underlying metabolic phenotype. Methods: We conducted a retrospective cohort study using the TriNetX research platform. Adult patients (≥18 years) prescribed GLP-1RAs (liraglutide or semaglutide) were stratified into two cohorts: obese patients (BMI ≥30) and diabetic non-obese patients (BMI < 30). Individuals with prior psychiatric diagnoses, substance use, or relevant comorbidities were excluded. Propensity score matching (1:1) was used to balance baseline demographics and clinical covariates. The primaryoutcomes were new-onset major depressive disorder (MDD), anxiety, and suicidal ideation or attempts. Relative risk (RR), 95% confidence intervals (CI), p-values, and risk differences were reported. Results: Compared to diabetic non-obese patients, obese patients on GLP-1RAs demonstrated significantly higher risk of psychiatric disorders. For MDD, the relative risk was 0.573 (95% CI: 0.461–0.714; p < 0.0001) with a risk difference of -2.454%. For anxiety, the relative risk was 0.552 (95% CI: 0.465–0.655; p < 0.0001) and the risk difference was -4.2%. There was no statistically significant difference in suicidal ideation or attempts between the two cohorts (p =1), with both the relative risk and risk difference indicating no effect. Discussion: Obese patients treated with GLP-1RAs had a significantly higher risk of developing major depressive disorder and anxiety compared to diabetic non-obese patients on the same therapy. These results suggest that obesity itself may confer increased psychiatric vulnerability in the context of GLP-1RA use. However, no difference in suicidal ideation or behavior was observed. These findings warrant further investigation and support the need for psychiatric screening in high-risk populations prior to GLP-1RA initiation.
Disclosures: Budoor Alqinai indicated no relevant financial relationships. Ayowumi Adekolu indicated no relevant financial relationships. Olanrewaju Adeniran indicated no relevant financial relationships. Vibhu Chittajallu indicated no relevant financial relationships. Soban maan indicated no relevant financial relationships. Shyam Thakkar indicated no relevant financial relationships. Shailendra Singh indicated no relevant financial relationships.
Budoor Alqinai, MBChB, MSc1, Ayowumi Adekolu, MD1, Olanrewaju Adeniran, MD2, Vibhu Chittajallu, MD3, Soban maan, MD1, Shyam Thakkar, MD1, Shailendra A. Singh, MD3. P0554 - Psychiatric Risk in Obese vs. Diabetic Non-Obese Patients on GLP-1 Receptor Agonists: A Retrospective Cohort Study, ACG 2025 Annual Scientific Meeting Abstracts. Phoenix, AZ: American College of Gastroenterology.
