Nicotine pouches and clinical outcomes related to smoking cessation: A systematic review of randomized trials.

Background and aims: Tobacco-free nicotine pouches (NPs) are oral nicotine products promoted by manufacturers and some researchers as tools that may reduce nicotine cravings and support smoking reduction or cessation. However, evidence regarding their actual clinical impact remains limited. This review aimed to evaluate the potential clinical effects of NPs in the context of smoking cessation, specifically focusing on user satisfaction, smoking urges and cigarette reduction compared with other nicotine and tobacco products.

Design: Systematic review of randomized trials conducted in adult smokers or nicotine users, reported according to PRISMA 2020 guidelines and registered in PROSPERO.

Setting: Studies conducted in high-income countries across Europe and North America were included, with data collected up to March 2024.

Participants/cases: Seven trials involving a total of 269 adult participants (≥18 years), including current smokers and users of other nicotine products. The review focused on tobacco-free NPs containing varying nicotine strengths and flavors. NPs were compared individually to multiple specific comparators across trials, including cigarettes, snus, nicotine gum and placebo, rather than being combined into a single comparator group.

Measurements: The primary outcomes were user satisfaction, urges to smoke and changes in cigarette consumption, considered the most important outcomes for assessing the potential of NPs in smoking cessation.

Findings: NPs were rated more favorably for satisfaction and product liking than gum or placebo, but consistently less than cigarettes (e.g. intent to reuse 14-46% for NPs vs. 57% for cigarettes). In one pilot randomized controlled trial, daily cigarette use decreased from 15.0 to 8.3 cigarettes/day over 8 weeks with 4 mg NPs (P = 0.01), with dependence scores also reduced (3.1 to 2.4, P = 0.02). Across studies (n = 7, sample sizes 24-63), none demonstrated a statistically significant increase in smoking cessation compared with control, snus or gum. Adverse events were mostly mild (e.g. cough, throat irritation, headache) and more frequent at higher NP doses, but no serious adverse events were reported. Meta-analysis was not performed due to heterogeneity in study designs and outcomes.

Conclusions: Tobacco-free nicotine pouches appear to be well tolerated and may reduce cigarette consumption compared with control, with effects similar to those seen with snus or nicotine gum. However, there is currently no statistically significant evidence that NPs increase rates of smoking cessation compared with other products or control.