Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review…

ReviewDrug and alcohol dependence· Jul 2026

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

Ying Xie, Yingman Gao, Xinmei Zhou … Chen Wang

Addiction MedicineReviewQ1IF 3.6

Slow nicotine metabolizers quit smoking more with non-titratable nicotine replacement therapy

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

Ying Xie … Chen Wang

Drug and alcohol dependence · Jul 2026

Background

Emerging evidence suggests that the nicotine metabolite ratio (nicotine metabolite ratio) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear.

Purpose

This study aims to investigate how nicotine metabolite ratio affects cessation outcomes under different medications to guide personalized treatment.

Methods

We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with nicotine metabolite ratio data.

n = 5 studies

Results

normal or fast metabolizers were less likely to quit than slow metabolizers

OR 0.81 (95% CI 0.68 to 0.96)

null 1

0.68

0.96

CI excludes the null - significant

More results

No significant associations were shown between normal/fast and slow metabolizers using titratable nicotine replacement therapy (OR=1.04, 95% CI=0.95-1.14; 2 studies, I²=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I²=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I²=59.8%).

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Conclusion · 1 of 2

Current evidence demonstrates that nicotine metabolite ratio moderates' treatment efficacy among those who smoke using non-titratable nicotine replacement therapy, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers.

Conclusion · 2 of 2

Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

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