Background: Based on randomized controlled trials, a network meta-analysis was conducted to compare treatment effects across varenicline and related smoking interventions. Methods: English databases were screened for randomized controlled trials reporting the effect of varenicline as treatment for smoking. The risk of bias in included trials was assessed using the Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and the GRADE approach was used to assess the evidence credibility on the tobacco treatment effects of different interventions. Results: Thirty-four studies involving 26,130 smokers were included in the network meta-analysis. Varenicline and 11 other interventions were reported, yielding 66 pairs of comparisons. Network meta-analysis showed that varenicline monotherapy or its combination with other interventions were superior in achieving smoking cessation compared to bupropion, nicotine replacement therapy, counselling, and placebo. Furthermore, compared to the varenicline, evident abstinence superiority was found in varenicline + bupropion (odds ratio = 1.49, 95% confidence interval [1.02, 2.18]). Finally, the surface under the cumulative ranking curve value indicated that varenicline + bupropion has the highest probability to become the best intervention. Conclusions: Varenicline monotherapy increased the odds of smoking cessation further than bupropion monotherapy, nicotine replacement therapy, counselling, and placebo, while varenicline combined with other interventions may even achieve a better abstinence effect. More credible evidence has been reported indicating that the combination of varenicline and bupropion is a superior treatment for smoking.

Objective: A network meta-analysis based on randomized controlled trials was conducted to investigate the effects of pharmacological interventions on smoking cessation. Methods: English databases were searched to obtain randomized controlled trials reporting the effect of pharmacological interventions on smoking cessation. The risk of bias for the included trials was assessed using Cochrane Handbook tool. Stata 15.1 software was used to perform network meta-analysis, and GRADE approach was used to assess the evidence credibility on the effects of different interventions on smoking cessation. Results: A total of 159 studies involving 60,285 smokers were included in the network meta-analysis. The analysis involved 15 interventions and which yielded 105 pairs of comparisons. Network meta-analysis showed that varenicline was more helpful for smoking cessation than other monotherapies, such as nicotine replacement therapy [Odds Ratio (OR) = 1.42, 95% confidence interval (CI) (1.16, 1.73)] and bupropion [OR = 1.52, 95% CI (1.22, 1.89)]. Furthermore, combined interventions were superior to monotherapy in achieving smoking cessation, such as varenicline plus bupropion over bupropion [OR = 2.00, 95% CI (1.11, 3.61)], varenicline plus nicotine replacement therapy over nicotine replacement therapy [OR = 1.84, 95% CI (1.07, 3.18)], and nicotine replacement therapy plus mecamylamine over naltrexone [OR = 6.29, 95% CI (1.59, 24.90)]. Finally, the surface under the cumulative ranking curve value indicated that nicotine replacement therapy plus mecamylamine had the greatest probability of becoming the best intervention. Conclusion: Most pharmacological interventions demonstrated a benefit in smoking cessation compared with placebo, whether monotherapy or combination therapy. Moreover, confirmed evidence suggested that some combination treatments, such as varenicline plus bupropion and nicotine replacement therapy plus mecamylamine have a higher probability of being the best smoking cessation in

Objective: A network meta-analysis (NMA) was conducted to investigate the effect of varenicline (VAR), bupropion (BUP), and nicotine replacement therapy (NRT) on smoking cessation. Methods: Eight databases were searched in May 2021, and only randomized controlled trials (RCTs) using varenicline, bupropion, or NRT (single or combined) for smoking cessation were included. The risk of bias in the included RCTs was assessed using the Cochrane Handbook tool. Stata 15.1 software was used to perform NMA, and the quality of the evidence was evaluated using Confidence in Network Meta-analysis (CINeMA). Findings: Twenty RCTs involving 16,702 smokers were included. The risk of bias results showed that 10 RCTs were rated as high, three were low, and seven were unclear. A total of 21 pairs were compared based on seven interventions. The NMA showed that, compared to the placebo (PLA), the other six interventions had significant efficacy in smoking cessation, where VAR + BUP showed the best effect of all treatments (odds ratio (OR) = 6.08, 95% confidence interval (CI) [3.47, 10.66]). Moreover, VAR + BUP was superior to VAR + NRT (OR = 1.66, 95% CI [1.07, 2.59]) and the three monotherapies (VAR, BUP, and NRT). In the monotherapies, the results of pairwise comparisons of VAR, BUP, and NRT did not show significant differences. Finally, the surface under the cumulative ranking curve (SUCRA) value indicated that VAR + BUP had the greatest probability of becoming the best intervention. Conclusions: The efficacy of VAR, BUP, and NRT alone increased the odds of smoking abstinence better than the placebo, combined interventions were superior to monotherapy, and VAR combined with other interventions had a better smoking cessation effect.