Comparing the Efficacy and Safety of Different Varenicline Dosing Strategies for First-Line Cigarette Smoking Cessation: A Network Meta-Analysis
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Abstract
Introduction: Tobacco use causes more than eight million deaths annually, requiring effective cessation strategies. Varenicline is a highly effective smoking cessation pharmacotherapy, but optimal dosing strategies remain debated. This network meta-analysis compares the efficacy and safety of alternative varenicline regimens (e.g., standard, extended duration, flexible dosing) to guide personalised treatment.
Method: Literature search was conducted across seven databases up to February 17, 2025. Quality appraisal was performed with the Cochrane Risk of Bias Tool 2. A bayesian network meta-analysis using the “BUGSnet” package in R using a random-effects model with relative risk (RR) and 95% credible intervals (CrI) was conducted. A sensitivity analysis excluded studies in comorbid populations, those with a high risk of bias, and those without counselling to obtain more coherent and generalisable estimates for healthy adult smokers.
Result: Twenty-nine randomised controlled trials (RCTs) were included. All varenicline dosing strategies were effective at the end of their respective treatment periods. However, 12 weeks of 1 mg twice-daily (BID) was most certain to be effective for smokers with comorbidity (RR: 1.79; 95% CrI: 1.49 – 2.11) at 52 weeks follow-up. In the sensitivity analysis with comorbidity excluded, 52 weeks of 1 mg BID for healthy adult smokers maintained statistically significant efficacy at 52 weeks follow-up and ranked as the most effective dose (RR: 4.93; 95% CrI: 1.91-10.97). There were no statistically significant differences in safety between the varenicline doses.
Conclusion: The most effective and safe varenicline monotherapy dosing strategy was 52 weeks of 1 mg BID for healthy adult smokers and 12 weeks of 1 mg BID for smokers with comorbidity. Further RCTs are needed to strengthen the evidence for the 52-week of 1mg BID regimen, and RCTs conducted in comorbid populations to strengthen generalisability and support potential updates to current clinical guidelines.
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