Semaglutide for Post-Smoking Cessation Weight Management

NCT06173778 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HSC-MS-23-0485
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 2

Brief Summary

This trial will examine the effect of semaglutide 2.4mg on changes in body weight, body composition, and peripheral and central mechanisms that control appetite, satiety, and food intake in the context of smoking cessation.

Conditions

Obesity; Overweight; Cigarette Smoking

Keywords

smoking; quit smoking; cigarettes; tobacco; overweight; obesity; obesity medications; semaglutide

Outcome Measures

Primary Outcomes (1)

• Change in Body Weight Percent

  Baseline to Week 28

Secondary Outcomes (3)

• Change in body weight as measured in kilograms (kg)

  Baseline to Week 28

• Change in body fat mass as measured in kilograms (kg)

  Baseline to Week 28

• Change in waist circumference as measured in centimeters(cm)

  Baseline to Week 28

Study Arms (2)

semaglutide

EXPERIMENTAL

Drug: semaglutide 2.4mg; Drug: Nicotine Replacement Therapy (NRT, nicotine patch); Behavioral: Brief Smoking Cessation Counseling

placebo

PLACEBO COMPARATOR

Drug: Placebo; Drug: Nicotine Replacement Therapy (NRT, nicotine patch); Behavioral: Brief Smoking Cessation Counseling

Interventions

Nicotine Replacement Therapy (NRT, nicotine patch) DRUG

Participants who smoke \>10 cigarettes/day will use 21 mg patches for the first 6 weeks, 14 mg patches during weeks 7 and 8, and 7 mg patches during weeks 9 and 10. Participants who smoke 5-10 cigarettes per day will use 14 mg patches for the first 6 weeks and 7 mg patches for weeks 7-10.

placebo; semaglutide

Brief Smoking Cessation Counseling BEHAVIORAL

Participants will receive weekly, manual-based individual smoking cessation counseling. Counseling will be provided by master's level clinicians.

placebo; semaglutide

semaglutide 2.4mg DRUG

Semaglutide 2.4mg will be self-administered once a week under the surface of the skin and will be started at 0.24mg once a week for 4 weeks; in 4-week intervals, the dose will be increased until a dose of 2.4mg is reached

semaglutide

Placebo DRUG

Non-active medication, self-administered

placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.
• 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:
• benzodiazepines

Sponsors & Collaborators

• The University of Texas Health Science Center, Houston: lead

Study Sites (2)

The University of Texas at Austin

Austin, Texas, 78723, United States

RECRUITING

The University of Texas Health Science Center at Houston

Houston, Texas, 77054, United States

RECRUITING

Related Publications (1)

• Yammine L, Leidy H, Maki KC, Weaver MF, Bodalski EA, Schmitz JM. A randomized controlled trial of once-weekly semaglutide for limiting post-smoking cessation weight gain in smokers with overweight/obesity: Study protocol. Contemp Clin Trials. 2025 Aug;155:107989. doi: 10.1016/j.cct.2025.107989. Epub 2025 Jun 18.

  PMID: 40554081 DERIVED

MeSH Terms

Conditions

Obesity; Overweight; Cigarette Smoking; Smoking

Interventions

semaglutide; Nicotine Replacement Therapy; Tobacco Use Cessation Devices

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Tobacco Smoking; Behavior; Tobacco Use

Intervention Hierarchy (Ancestors)

Drug Therapy; Therapeutics

Study Officials

• Luba Yammine, PhD

  The University of Texas Health Science Center, Houston

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Luba Yammine, PhD

CONTACT

713-486-2737; Luba.Yammine@uth.tmc.edu

Jessica Vincent

CONTACT

713-486-2803; Jessica.N.Vincent@uth.tmc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 18, 2023
• Study Start: April 23, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)