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

Obesity (Silver Spring, Md.) Pub Date : 2025-09-15 DOI:10.1002/oby.70024

Hao Dai, Rotana M Radwan, Grant D Scheiffele, Huilin Tang, Amy Sheer, Hsin-Yueh Lin, Pengyue Zhang, Darlene Adirika, Kate Luong, Jiang Bian, Jingchuan Guo

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Abstract

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.

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GLP-1受体激动剂和老年2型糖尿病患者的物质使用障碍：一项目标试验模拟

目的：胰高血糖素样肽-1受体激动剂（GLP-1RAs）被批准用于2型糖尿病（T2D）和肥胖，可能调节奖励通路并减少物质相关行为。本研究评估了GLP-1RA的使用与并存T2D和物质使用障碍（SUD）的老年人物质使用相关住院之间的关系。方法：一项使用2016-2020年Medicare数据的回顾性队列研究比较了GLP-1RA启动者与年龄≥65岁的SGLT2抑制剂（SGLT2is）或DPP-4抑制剂（DPP4is）新使用者。主要结局是任何SUD的住院治疗；次要结局包括因酒精使用障碍（AUD）和阿片类药物使用障碍（OUD）住院。倾向评分1:1匹配和Cox比例风险模型在意向治疗方法下使用。结果：在GLP-1RA与DPP4i队列（n = 4920）中，GLP-1RA使用者的SUD住院风险（HR 0.76; 95% CI, 0.67-0.86）和OUD住院风险（HR 0.64; 95% CI, 0.43-0.96）较低，AUD住院风险（HR 0.76; 95% CI, 0.53-1.08）无显著趋势（HR 0.76; 95% CI, 0.53-1.08）。与SGLT2is相比，未观察到显著差异（n = 4620）。结论：在老年T2D患者中，GLP-1RA的使用与DPP4i的使用相比，与SUD相关的住院率降低有关，这表明可能会改变SUD治疗的目的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Obesity (Silver Spring, Md.)

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