Exenatide Once Weekly for Smoking Cessation: A Randomized Clinical Trial

Background: Cigarette smoking is the greatest preventable cause of morbidity and premature mortality in the US. Approved pharmacological treatments for smoking cessation are only marginally effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 (GLP-1) is produced in the intestinal L-cells and in the hindbrain nucleus solitarius. GLP-1 functions to maintain glucose homeostasis and to reduce food intake. Several GLP-1 agonists are used clinically for the treatment of type 2 diabetes and obesity. In addition to these actions, GLP-1 agonists have recently been shown in preclinical studies to attenuate consumption of alcohol and several drugs of abuse, including nicotine. Aims: Our primary aims are 1) to examine the impact of treatment with weekly extended-release injectable exenatide on smoking abstinence and 2) to assess whether exenatide treatment is associated with the reduction in craving and withdrawal symptoms. This is the first clinical study of exenatide as a treatment for smoking cessation. Methods: We are enrolling smokers (n=90) with pre-diabetes who desire to quit smoking and are willing to make a quit attempt during the course of the study. Participants will be randomized 1:1 to receive once weekly exenatide or placebo. All participants will receive transdermal nicotine replacement therapy (NRT) and behavioral counseling. Biochemically verified abstinence from smoking, craving for cigarettes, withdrawal symptoms, and fasting blood glucose levels will be assessed during and following 6 weeks of treatment. Expected Outcomes: We hypothesize that: 1) exenatide treatment will increase the number of participants able to achieve complete smoking abstinence above that achieved via standard NRT and 2) exenatide will reduce craving and withdrawal symptoms. Craving and withdrawal symptoms predict long-term efficacy, which we hope to examine in a follow-up study. Funding sources: The funding for this study is provided by the University of Texas Health Science Center at Houston CCTS Scholar Award and PARTNERS Research Awards (Dr. Luba Yammine)