GLP-1RA AND RISK OF INCIDENT OPIOID USE DISORDER IN T2D: IMPLICATIONS FOR DRUG REPURPOSING
Author(s)
Amina Alkhalaf, PharmD, MS1, Hillary Samples, PhD, MHS2, Greta Bushnell, PhD, MSPH2, Kimberly O’Malley, MS1, Chintan Dave, PharmD, PhD1;
1Center for Health Outcomes, Policy, and Economics, Ernest Mario College of Pharmacy, Piscataway, NJ, USA, 2Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA
1Center for Health Outcomes, Policy, and Economics, Ernest Mario College of Pharmacy, Piscataway, NJ, USA, 2Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Health Care Policy and Aging Research, Rutgers University, New Brunswick, NJ, USA
OBJECTIVES: Building on preclinical and early clinical evidence suggesting that Glucagon-Like Peptide-1 Receptor Agonists (GLP-1RA) may attenuate reward-related behaviors and reduce susceptibility to opioid use disorders (OUD), this study tested the hypothesis whether GLP-1RAs reduce the risk of incident OUD among patients with T2D receiving prescription opioids.
METHODS: We conducted a cohort study using a large commercial claims database (2014-2023) among adults with T2D receiving long-term opioid therapy at the time they initiated GLP-1RA or sodium-glucose cotransporter 2 inhibitors (SGLT2i). Long-term opioid therapy was defined as≥90 days of opioid use in the 356 days preceding initiation and overlapping with the index date. SGLT2i was chosen as the active comparator given their similar second-line use and neutral effects on OUD.The primary outcome was incident OUD diagnosis defined with ICD-9-CM/ICD-10-CM codes, with opioid-involved overdose evaluated as a secondary outcome. Cox proportional hazards models were used to estimate adjusted Hazard Ratios (aHR), with propensity score inverse probability of treatment weighting applied.
RESULTS: The study cohort comprised 7,456 patients on long-term opioid treatment starting GLP-1RA or SGLT2i treatment (mean [SD] age, 54.2 [7.2] years; 53.4% female). Among GLP-1RA initiators, 37 persons were newly diagnosed with OUD (adjusted incidence rate [IR] per 1,000 person-years: 9.7) compared with 30 events among SGLT2i initiators (IR 8.9) over a median follow-up time of 209 days [IQR, 344], corresponding to an aHR of 1.03 (95% CI:0.64-1.66). No difference in the risk of opioid-involved overdose was observed for GLP-1RA vs. SGLT2i initiators (aHR 0.91, 95% CI 0.39-2.11). Findings were consistent across sensitivity and subgroup analyses.
CONCLUSIONS: The study findings may not be generalizable to non-commercially insured populations. Among US commercially insured adults with T2D receiving long-term prescription opioid treatment, GLP-1RA use was not associated with a reduction in risk of incident OUD or opioid overdose.
METHODS: We conducted a cohort study using a large commercial claims database (2014-2023) among adults with T2D receiving long-term opioid therapy at the time they initiated GLP-1RA or sodium-glucose cotransporter 2 inhibitors (SGLT2i). Long-term opioid therapy was defined as≥90 days of opioid use in the 356 days preceding initiation and overlapping with the index date. SGLT2i was chosen as the active comparator given their similar second-line use and neutral effects on OUD.The primary outcome was incident OUD diagnosis defined with ICD-9-CM/ICD-10-CM codes, with opioid-involved overdose evaluated as a secondary outcome. Cox proportional hazards models were used to estimate adjusted Hazard Ratios (aHR), with propensity score inverse probability of treatment weighting applied.
RESULTS: The study cohort comprised 7,456 patients on long-term opioid treatment starting GLP-1RA or SGLT2i treatment (mean [SD] age, 54.2 [7.2] years; 53.4% female). Among GLP-1RA initiators, 37 persons were newly diagnosed with OUD (adjusted incidence rate [IR] per 1,000 person-years: 9.7) compared with 30 events among SGLT2i initiators (IR 8.9) over a median follow-up time of 209 days [IQR, 344], corresponding to an aHR of 1.03 (95% CI:0.64-1.66). No difference in the risk of opioid-involved overdose was observed for GLP-1RA vs. SGLT2i initiators (aHR 0.91, 95% CI 0.39-2.11). Findings were consistent across sensitivity and subgroup analyses.
CONCLUSIONS: The study findings may not be generalizable to non-commercially insured populations. Among US commercially insured adults with T2D receiving long-term prescription opioid treatment, GLP-1RA use was not associated with a reduction in risk of incident OUD or opioid overdose.
Conference/Value in Health Info
2026-05, ISPOR 2026, Philadelphia, PA, USA
Value in Health, Volume 29, Issue S6
Code
EPH58
Topic
Epidemiology & Public Health
Disease
SDC: Diabetes/Endocrine/Metabolic Disorders (including obesity)