PMID-40554081 — Yammine: Semaglutide for Post-Smoking-Cessation Weight Gain (Phase 2 Protocol)

[DRAFT — authored 2026-04-20. Citation verified against PubMed 2026-04-20.]

Citation

Yammine L, et al. 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;155:107989. doi: 10.1016/j.cct.2025.107989. PMID: 40554081.

External URL: PubMed

Study Design

Type: Study protocol paper (not primary results)
Design: Parallel group, two-arm, double-blind, placebo-controlled RCT
N (planned): 177 smokers with overweight or obesity
Allocation: 2:1 (semaglutide : placebo)
Intervention: Semaglutide 2.4 mg weekly SC × 28 weeks (16-week dose escalation + 12 weeks at target dose) + placebo arm
Co-interventions: All participants receive 10 weeks of nicotine-replacement therapy (nicotine patches) + brief smoking-cessation counseling

Key Elements

Primary outcome

Weight change percentage at treatment completion — designed to measure the post-smoking-cessation weight gain that commonly discourages sustained cessation in smokers with overweight/obesity

Secondary outcomes

Absolute weight change
Fat mass change
Waist circumference change

Exploratory outcomes

Dietary patterns
Smoking abstinence rates (Phase 2 signal on cessation efficacy, though not primary)

Clinical Relevance

Yammine 2025 is a protocol paper for a Phase 2 trial designed to address a specific clinical problem: post-smoking-cessation weight gain is a major barrier to sustained cessation in overweight/obese smokers. Core points:

Dual-benefit hypothesis: If semaglutide can limit post-cessation weight gain while also modulating tobacco craving (per Wang 2024 real-world observational signal, PMID 39074369), it may become a useful adjunct to smoking-cessation pharmacotherapy.
Protocol-paper status: Primary results are not yet published as of April 2026. The protocol paper establishes methodology, power calculations, and outcome definitions for the future results publication.
Cross-reference to AUD: Parallels Hendershot Phase 2 AUD RCT (PMID 39937469) — both Phase 2 trials testing semaglutide in reward-regulation/addiction indications.
Not yet evidence-based indication: Smoking cessation is NOT an FDA-approved indication for semaglutide. Current use for this purpose would be off-label and not recommended outside a research protocol.

Linked Peptides

Semaglutide

Related Lessons

Lesson 5.2 — Semaglutide Deep Dive (Emerging Indications)

Related Studies

PMID-39074369 – Wang Semaglutide Tobacco Use Disorder Ann Intern Med — real-world observational TUD signal
PMID-39937469 – Hendershot Semaglutide Alcohol Use Disorder RCT — AUD Phase 2 (completed)

PMID-40554081 – Yammine Semaglutide Smoking Cessation Protocol