Association between GLP-1 receptor agonist use and substance use disorders among individuals with type 2 diabetes or obesity: a nested case-control study in the All of Us research program.

OBJECTIVES

The current study evaluated the association between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and substance use disorders (SUD) in type 2 diabetes and obesity.

METHODS

We conducted a retrospective nested case-control study using the All of Us Research Program data. Cases were defined as diabetes/obese individuals with a new diagnosis of alcohol use disorder (AUD), opioid use disorder (OUD), nicotine use disorder (NUD), or cocaine use disorder (CUD). Control participants were drawn from individuals with diabetes or obesity who had no documented history of SUD. Conditional logistic regression was performed to estimate the association between SUD and GLP-1 RA exposure.

RESULTS

The study included a total of 22,652 participants in the AUD group, 13,226 in the OUD group, 42,320 in the NUD group, and 9,296 in the CUD group; each group comprised both cases and matched control participants. GLP-1 RA use was associated with a 74% reduction in the odds of AUD (odds ratio [OR] = 0.26; 95% confidence interval [CI]: 0.20-0.34), a 69% reduction in the odds of OUD (OR = 0.31; 95% CI: 0.23-0.42), a 68% reduction in the odds of NUD (OR = 0.32; 95% CI: 0.27-0.39), a 75% reduction in the odds of CUD (OR = 0.25; 95% CI: 0.16-0.40), and 75% lower odds of any SUD compared with non-users participants (OR = 0.25, 95% CI 0.22-0.30).

CONCLUSIONS

GLP-1 RA use was consistently associated with lower odds of developing SUDs among individuals with type 2 diabetes or obesity. These findings suggest potential for GLP-1 RAs to help mitigate SUD in these populations.