Glucagon-like peptide-1 receptor agonists are associated with reduced risk of developing substance use disorders

1. Use of glucagon-like peptide-1 (GLP-1) receptor agonists was associated with reduced risk of developing substance use disorders among US veterans with type 2 diabetes.

Evidence Rating Level: 2 (Good)

Glucagon-like peptide-1 (GLP-1) receptor agonists have been associated with reduced risks of incident substance use disorders (SUDs) such as alcohol use and incident cannabis use disorder. However, the link between GLP-1 receptor agonists and risks of other SUDs, such as opioid use disorder and stimulant use disorder are unclear. This study thus investigated the relationship between initiation of GLP-1 receptor agonists and risk of incident SUDs across a range of substances in people with no history of SUDs. This cohort study emulated a set of eight parallel, new user target trials using the US Department of Veterans Affairs electronic health records and included veterans aged >18 and a diagnosis of type 2 diabetes. Participants were assigned to one of the two protocols: people without pre-existing SUD in protocol 1 and people with pre-existing SUD in protocol 2. For both protocols, treatment strategies of initiating a GLP-1 receptor agonist versus a sodium-glucose cotransporter-2 (SGLT-2) inhibitor were compared. Patients were followed for up to three years. The main outcomes of incident SUDs were alcohol, cannabis, cocaine, nicotine, opioid, other SUDs, and a composite of these outcomes. Out of the 524,817 participants included in Protocol 1, 124,001 initiated GLP-1 receptor agonists and or 400,816 initiated SGLT-2 inhibitors. Out of the 81,617 participants included in Protocol 2, 16,768 initiated GLP-1 receptor agonists, and 64,849 initiated SGLT-2 inhibitors. Compared with initiation of SGLT-2 inhibitors, initiation of GLP-1 receptor agonists was associated with 18% lower risk of alcohol use disorders (hazard ratio [HR], 0.8295%; 95% CI, 0.78 to 0.85), 14% lower risk of cannabis use (HR, 0.86; 95% CI, 0.81 to 0.90), 20% lower risk of cocaine use (HR, 0.80; 95% CI, 0.72 to 0.88), 20% lower risk of nicotine use (HR, 0.80; 95% CI, 0.74 to 0.87), 25% lower risk of opioid use (HR, 0.75; 95% CI, 0.67 to 0.85), 13% lower risk of other SUDs (HR, 0.87; 95% CI, 0.81 to 0.94), and 14% lower risk of composite outcome of all incident SUDs (HR, 0.86; 95% CI, 0.83 to 0.88). Overall, this study found that initiating GLP-1 receptor agonists was associated with reduced risk of developing various SUDs, highlighting its potential in the prevention of SUDs. 

Click here to read this study in BMJ

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