Importance Glucagon-like peptide-1 (GLP-1) therapies have revolutionized the management of chronic conditions like obesity and diabetes. Consistent with the overlap between feeding and metabolic pathways and those mediating addictive behaviors, growing evidence suggests that GLP-1 therapies may also be beneficial for treating alcohol and other substance use disorders (ASUDs). This review discusses the current landscape of GLP-1 therapies in the context of ASUDs, mental health considerations, and gaps and opportunities in this field. Observations Preclinical evidence across several experimental models and species consistently shows that GLP-1 receptor agonists (GLP-1RAs) reduce drug intake and other addictive behaviors. Research to date has primarily focused on alcohol; however, nicotine, opioids, and psychostimulants have also been studied. Observational cohort studies using electronic health records suggest improvements in ASUD-related outcomes among people treated with GLP-1RAs for other indications. Randomized clinical trials (RCTs) have been limited, yielding mixed results but overall promising signals. Several RCTs are ongoing or about to start. Despite some early pharmacovigilance alarms, GLP-1RAs do not seem to cause or increase the risk of psychopathology (eg, depression, suicidal ideation and/or behavior). Some recent studies suggest beneficial effects of GLP-1RAs on mental health outcomes, but more work is needed. Conclusions and Relevance The rationale for studying GLP-1 therapies for ASUDs is supported by preclinical and observational clinical evidence. RCTs are emerging and critically needed at this juncture to determine the safety and efficacy of GLP-1 therapies in people with ASUDs. Pending results from RCTs, GLP-1 therapies have the potential to be repurposed for ASUDs. However, there are several relevant questions in need of further investigation, including the specifics of treatment with GLP-1 therapies in the context of addiction (eg, dose, duration, tachyphylaxis, impact of discontinuation), individual differences and potential predictors of response, mechanisms of action, intersection with mental health and medical comorbidities, cost, and fair access to these treatments.
Farokhnia et al. (Wed,) studied this question.