The purpose of this study is to determine if exenatide improves end-of-treatment smoking abstinence rates and to determine if exenatide mitigates post-cessation weight gain.

Inclusion Criteria:

• Be willing and able to sign and date an informed consent form, willing to comply with all study procedures, and be available for the duration of the study
• Male or female, 18-75 years of age
• Have been smoking ≥5 cigarettes per day for at least 1 year and provide positive cotinine test
• Desire to quit smoking (defined as "intend to quit within one month")
• Have HbA1C levels between 5.7 and 6.4% and/or a body mass index of ≥25 kg/m2
• Have vital signs as follows: resting pulse between 50 and 95 bpm, BP between 90-150 mmHg systolic and 45-95 mmHg diastolic
• Have hematology and chemistry laboratory tests that are within reference limits (±10%), with the following exception: pancreatic tests (lipase and amylase) must be within normal limits
• Agree (if the subject is female and of child-bearing potential) to use at least one of the following methods of birth control from time of the first administration of the study medication to at least 7 days post the last dose of the study medication, unless the partner is surgically sterile (underwent vasectomy): oral contraceptives, contraceptive sponge, patch, double barrier (diaphragm/spermicidal or condom/spermicidal), intrauterine contraceptive system, etonogestrel implant, medroxyprogesterone acetate contraceptive injection, hormonal vaginal contraceptive ring, or complete abstinence from sexual intercourse.
• Women of child-bearing potential must provide negative urine pregnancy tests prior to randomization
• Have a medical history and a brief physical examination demonstrating no clinically significant contraindications for study participation, in the judgment of the Study Physician and the PI.

Exclusion Criteria:

• Psychoactive substance abuse or dependence (excluding nicotine dependence) within the past 3 months (existing diagnosis or as determined by the structured interview)
• Currently using chewing tobacco, snuff, snus or electronic cigarettes
• Currently enrolled in a smoking cessation program/research study or using pharmacotherapy for smoking cessation (NRT, varenicline, or bupropion)
• Currently enrolled in a behavioral weight management plan/research study, or taking medication used for weight management (i.e., orlistat, lorcaserin,*naltrexone-bupropion, liraglutide, phentermine, benzhetamine, diethylpropion, phendimetrazine), or medication known to impact weight (i.e., corticosteroids) *Note: Withdrawn from the market in Feb 2020, but some patients may still be taking it
• Currently using oral or injectable glucose lowering medications
• Urine drug test positive, before randomization, for any of the following substances: benzodiazepines, cocaine, opioids,*amphetamines, methamphetamine, buprenorphine, barbiturates, 3,4-methylenedioxy-methamphetamine (MDMA), and/or THC. *Note: If positive for opioids or oxycodone but recent opioid use for acute pain is reported by the study candidate, then the candidate can be included at the discretion of the Primary Investigator and/or Study Physician
• Psychotic or bipolar disorder, or mood disorder with psychotic features, or eating disorder (existing diagnosis or as determined by the structured interview)
• Moderate to high risk for suicidality (as determined by the structured interview)
• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN2)
• Type 1 or type 2 diabetes mellitus (previously diagnosed or indicated by HbA1C level of ≥6.5%)
• Severe cardiovascular disease (history of myocardial infarction, life-threatening arrhythmia, or worsening angina pectoris)
• Severe gastrointestinal disease (i.e., severe gastroparesis)
• Previous history of pancreatitis or risk of pancreatitis
• Creatinine clearance <45 mL/min or end stage renal disease (ESRD)
• Previous medically adverse reaction to the study medications or nicotine
• Women who are currently pregnant, or plan to become pregnant, or lactating, or of childbearing potential and are not using medically accepted forms of contraception. Medically accepted forms of contraception are specified in the inclusion criterion 8.
• Current, anticipated, or pending enrollment in another research study over the next 6 months that could potentially affect subject safety and/or the study data/design as determined by the PI and/or Study Physician
• Unable to communicate (read, write, and speak) fluently in English
• Have any illness or condition which in the opinion of the PI and/or the Study Physician would preclude safe and/or successful completion of the study.