GLP-1 Receptor Agonists and Suicide Risk in Adults With Chronic Pain: A New User Cohort Across Multi-System EHR data
A. S. Verma, V. Sharma, A. Pathak, R. GuptaIntroduction
Suicidality is a significant concern in patients living with chronic pain, with suicidal ideation reported in 18-50% of this population, and 5-14% attempting suicide. GLP-1 receptor agonists (GLP-1RAs) reduce pain hypersensitivity by acting on peripheral and central nervous systems through glucagon-like peptide-1 (GLP-1) receptors. GLP-1R–based anti-obesity/diabetes therapies, can potentially be useful in high-risk groups such as those with chronic pain, a research gap we aim to fulfill through this cohort study.
Objectives
To compare 12-month risk of suicidality and related psychiatric/health-services outcomes among chronic-pain patients initiating GLP-1 therapies versus other anti-obesity medications (AOMs).
Methods
Retrospective cohort using TriNetX US Collaborative Network (72 HCOs). Adults (≥18) meeting a prespecified chronic-pain phenotype (ICD-10: G89.2x, G89.4, M79.7, chronic headache subtypes, vertebrogenic/other low-back pain, osteoarthritis subtypes) formed the base population. Exposure: GLP-1 agents (semaglutide, liraglutide, dulaglutide, exenatide, lixisenatide, tirzepatide); Comparator: non-GLP AOMs (orlistat, phentermine, bupropion, naltrexone, topiramate). Cohorts mutually excluded the other drug class. Index = first qualifying medication after pain documentation. Outcomes (12-month window, excluding prior outcome): suicidal ideation (R45.851), suicide attempt (T14.91*), any ED visit (CPT 99281–99285), and exploratory psychiatric outcomes (F32.9 depression, F41.9 anxiety, G47.00 insomnia, F11.20 opioid dependence). Propensity-score matching (1:1) balanced age, sex, ethnicity, type-2 diabetes, and BMI percentile.
Results
After matching (N=501,736 per arm) (Table 1), GLP-1 initiation was associated with lower risk of:
Suicidal ideation: RR 0.19 (95% CI 0.17–0.20); HR 0.21 (0.19–0.22).
Suicide attempt: RR 0.13 (0.10–0.17); HR 0.15 (0.11–0.19).
Any ED visit: RR 0.77 (0.76–0.79); HR 0.86 (0.84–0.88). Exploratory outcomes were concordant: depression RR 0.18, anxiety RR 0.42, insomnia RR 0.48, opioid dependence RR 0.25 (all p<0.001) (Table 2).
Image 1: Long description.