GLP‐1 Receptor Agonists and Substance Use Disorders in Older Adults With Type 2 Diabetes: A Target Trial Emulation

Sep 16, 2025Obesity (Silver Spring, Md.)

GLP-1 Receptor Agonists and Substance Use Disorders in Older Adults with Type 2 Diabetes

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GLP-1 Therapies on OpenScience ↗PubMed ↗DOI ↗

Abstract

GLP-1RA users had a lower risk of substance use disorder (SUD) hospitalization compared to DPP-4 inhibitor users, with a hazard ratio of 0.76.

GLP-1 receptor agonists may influence reward pathways and reduce substance-related behaviors.
In older adults with type 2 diabetes and substance use disorders, GLP-1RA use is linked to a reduced risk of SUD hospitalization.
A significant reduction in hospitalization for opioid use disorder (OUD) was observed in GLP-1RA users (HR 0.64).
There was a nonsignificant trend indicating lower hospitalization for alcohol use disorder (AUD) in GLP-1RA users (HR 0.76).
No significant differences in hospitalization rates for SUD were found when comparing GLP-1RA users to those on SGLT2 inhibitors.

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OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for type 2 diabetes (T2D) and obesity, may modulate reward pathways and reduce substance-related behaviors. This study assessed the association between GLP-1RA use and substance use-related hospitalization in older adults with coexisting T2D and substance use disorders (SUD).

METHODS: A retrospective cohort study using 2016-2020 Medicare data compared GLP-1RA initiators with new users of SGLT2 inhibitors (SGLT2is) or DPP-4 inhibitors (DPP4is) among adults aged ≥ 65. The primary outcome was hospitalization for any SUD; secondary outcomes included hospitalizations for alcohol use disorder (AUD) and opioid use disorder (OUD). Propensity score 1:1 matching and Cox proportional hazards models were used under an intention-to-treat approach.

RESULTS: In the GLP-1RA versus DPP4i cohort (n = 4920), GLP-1RA users had a lower risk of SUD hospitalization (HR 0.76; 95% CI, 0.67-0.86) and OUD hospitalization (HR 0.64; 95% CI, 0.43-0.96), with a nonsignificant trend for AUD (HR 0.76; 95% CI, 0.53-1.08). No significant differences were observed compared to SGLT2is (n = 4620).

CONCLUSIONS: Among older adults with T2D, GLP-1RA use was associated with reduced SUD-related hospitalization versus DPP4i use, suggesting potential repurposing for SUD management.