March 4, 2026

expert reaction to cohort study on GLP-1 receptor agonists and risk of substance use disorders among US veterans with type 2 diabetes

A cohort study published in The BMJ looks at GLP-1 use and the risk of substance use among US veterans with type 2 diabetes.

Dr Marie Spreckley, Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, MRC Epidemiology Unit, University of Cambridge, said:

“This is a large observational study using a target trial emulation framework within US Veterans Affairs electronic health records, comparing GLP-1 receptor agonists with SGLT-2 inhibitors in 606,434 adults with type 2 diabetes. The press release reflects the findings accurately. Initiation of a GLP-1 receptor agonist was associated with lower risks of several incident substance use disorders (SUDs), and with reduced adverse outcomes among those with pre-existing SUDs.

“Strengths include the new-user, active comparator design and the use of inverse probability weighting with cause specific Cox models, alongside subgroup and sensitivity analyses. However, this remains an observational study and residual confounding cannot be excluded. Although many variables were adjusted for, unmeasured factors such as severity of substance use or social determinants of health may still influence the results.

“Absolute differences were modest for several incident SUD outcomes, generally in the single digit range per 1000 people over three years, and larger for some adverse outcomes in those with pre-existing SUDs. The predominantly older male VA population may limit generalisability.

“The findings are biologically plausible but should be considered hypothesis generating. Randomised trials specifically assessing substance-related outcomes would be needed before these medicines could be considered treatments for substance use disorders. Established evidence based SUD treatments remain essential.”

‘Glucagon-like peptide-1 receptor agonists and risk of substance use disorders among US veterans with type 2 diabetes: cohort study’ by Miao Cai et al. was published in The BMJ at 23:30 hours UK time Wednesday 4 March 2026. 

DOI: http://dx.doi.org/10.1136/ bmj-2025-086886

Declared interests

Dr Marie Spreckley: “I am a postdoctoral researcher at the University of Cambridge working on obesity, incretin-based therapies and nutrition. I have no personal financial relationships with manufacturers of GLP-1 receptor agonists and have received no industry funding.”