Metabolic medicines and addiction: what GLP-1 receptor agonists might add to substance use care

Metabolic medicines and addiction: what GLP-1 receptor agonists might add to substance use careClinical trials and equitable care pathways are needed to build on early evidence of benefit Fares Qeadan associate professor of biostatistics Substance use disorders (SUDs) are common and burdensome for patients, families, and health systems, 1 2 yet effective albeit underused drugs exist for only some conditions. 2 3 Glucagon-like peptide-1 (GLP-1) receptor agonists, used to treat type 2 diabetes and obesity, 4 have been proposed as anti-craving agents because GLP-1 signalling interacts with brain reward and stress circuits. 5 In a linked paper, Cai and colleagues (doi:10.1136/bmj-2025-086886)tested this hypothesis using routinely collected healthcare data from US veterans with type 2 diabetes. 6 Using Veterans Affairs data, the authors emulated eight parallel target trials 6 7 comparing initiation of a GLP-1 receptor agonist with initiation of a sodium-glucose cotransporter-2 (SGLT-2) inhibitor; an active comparator with similar cardiometabolic indications.In veterans without a baseline SUD, initiation of a GLP-1 receptor agonist was associated with lower hazards of incident alcohol (hazard ratio 0.82), cannabis (0.86), cocaine (0.80), nicotine (0.80), opioid (0.75), and other SUDs (0.87) over three years, with net three year risk differences of roughly 1-6 fewer cases per 1000 people. 6 More clinically consequential were the findings among veterans with a pre-existing SUD, shifting the question from prevention to harm reduction.In this group, initiation of a GLP-1 receptor agonist was associated with fewer SUD related emergency department visits (hazard ratio 0.69), hospital admissions (0.74), and mortality (0.50), overdose (0.61), and suicidal ideation or attempt (0.75), translating to about 1-10 fewer events per 1000 people over three years. 6 These results suggest that any potential benefit is not restricted to a single diagnosis or substance and may extend to acute and life threatening consequences of addiction.