Inclusion Criteria:
- Ability to provide informed consent before any study-related activity, willing to comply with al study procedures, and be available for the duration of the study.
- Body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension (unless meets medical exclusion criterion 7), cardiovascular disease (unless meets medical exclusion criterion 6), dyslipidemia, or obstructive sleep apnea
- Have been smoking ≥5 cigarettes per day for at least 1 year (prior to screening) and provide positive cotinine test.
- Desire to quit smoking (defined as "intend to quit within one month")
- Agree (if the participant is female and of child-bearing potential) to use effective contraceptive methods, unless the participant's male partner(s) is surgically sterile (underwent vasectomy).
- Women of child-bearing potential must provide negative urine pregnancy tests prior to randomization.
- Normal cognitive restraint (assessed as cognitive restraint score of <4 from the Three Factor Eating Habits Questionnaire)
- 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 Principal Investigator
Exclusion Criteria:
Medical Exclusions
- Personal or first-degree relative(s) history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2).
- Acute pancreatitis within the past 6 months prior to screening.
- History or presence of chronic pancreatitis.
- Type 1 or type 2 Diabetes Mellitus (previously diagnosed or indicated by HbA1C ≥48 mmol/mol (6.5%) as measured by central laboratory at screening).
- End stage renal disease (ESRD, previously diagnosed or indicated by estimated glomerular filtration rate (eGFR) value of eGFR < 15 ml/min/1.73 m2 as measured by central laboratory at screening).
- Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischemic attack within the past 60 days prior to screening.
- Systolic blood pressure (SBP) >159 mmHg and/or diastolic blood pressure (DBP) >99 mmHg)
- History of malignant neoplasms within the past 5 years prior to screening. Basal and squamous cell skin cancer and any carcinoma in-situ are allowed.
- Severe gastrointestinal disease (i.e., severe gastroparesis).
- Known or suspected hypersensitivity to nicotine/nicotine patches; semaglutide, excipients, or related products.
- 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.
- Have any illness or condition which in the opinion of the Principal Investigator and/or the Study Physician would preclude safe and/or successful completion of the study.
Psychiatric / Substance Use Exclusions
- Psychoactive substance abuse or dependence (excluding nicotine dependence) within the past 3 months prior to screening (existing diagnosis or as determined by the structured interview).
- Urine drug test positive, before randomization, for any of the following substances:
1. benzodiazepines
2. cocaine
3. opioids
4. amphetamines
5. methamphetamine
6. buprenorphine
7. barbiturates
8. 3,4-methylenedioxy-methamphetamine (MDMA)
9. Tetrahydrocannabinol (THC)
- Psychotic or bipolar disorder, or mood disorder with psychotic features; or eating disorder (existing clinical diagnosis or as determined by the structured interview)
- Moderate to high risk for suicidality (as determined by the structured interview).
Weight-Related Exclusions
- Previously undergone bariatric surgery
- Gained/lost ≥4.5 kg over the past 6 months (prior to screening)
- Currently enrolled in a behavioral weight management plan
- Uncontrolled thyroid disease (the criterion will be assessed at the Study Physician's and the Principal Investigator's discretion)
Smoking-Related Exclusions
-Currently using other combustible (e.g., cigars), other (e.g., chewing tobacco, snuff, snus) or alternative (e.g., electronic cigarettes) tobacco products
Medication-Related Exclusions
- Currently using oral or injectable glucose lowering medications
- Currently using pharmacotherapy for smoking cessation (NRT, varenicline, or bupropion)
- Currently or recently (last 90 days prior to screening) taking medication used for weight management (i.e., orlistat, lorcaserin,vi naltrexone-bupropion, liraglutide, phentermine, topiramate, benzphetamine, diethylpropion, phendimetrazine)
- Currently or recently (within the past 14 days prior to screening) taking medication(s) known to impact appetite and/or weight (i.e., corticosteroids, excluding inhaled)
General Exclusions
- Current, anticipated, or pending enrollment in another research study during this trial that could potentially affect participant safety and/or the study data/design as determined by the Principal Investigator and/or Study Physician.
- Not planning to live in the area for the duration of this trial.
- Surgery scheduled for the duration of the trial, except for minor surgical procedures, in opinion of the Principal Investigator and/or the Study Physician.
- Unable to communicate (read, write, and speak) fluently in English.