Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder: A Case Series Study

Cocaine use remains a serious public health problem associated with a marked increase in overdose deaths in the past decade. No medications have yet been proven to be effective for the treatment of cocaine use disorder (CUD). Among the highly promising medications have been glucagon-like peptide 1 receptor agonists (GLP-1RA) that are currently used for the treatment of type 2 diabetes mellitus and weight management. Preclinically, GLP-1RAs have been shown to attenuate cocaine self-administration, however, this has not yet been demonstrated in a human laboratory study. The GLP-1RA extended-release exenatide is given as a once-weekly injection, which may be clinically advantageous for addressing medication nonadherence among individuals with CUD. Here, we assess feasibility and safety by reporting on 3 cases of patients with CUD who received 6 weeks of exenatide 2 mg subcutaneously once-weekly in an open-label fashion, along with standard individual drug counseling. We observed excellent attendance and compliance, along with positive end-of-study satisfaction ratings. The medication was well tolerated and without unexpected or severe adverse events. Results for cocaine use and related clinical effects were more mixed, yet encouraging. Future empirical testing of exenatide for treating CUD should utilize a randomized controlled trial design and longer treatment duration.