A Cochrane review identified 150 trials; 117 with over 50 000 participants contributing to the primary comparison between NRT and a placebo or non-NRT control group. The RR for abstinence for any form of NRT compared to control was 1.60 (95% CI 1.53 to 1.68). The RR for different forms of NRT were 1.49 (95% CI 1.40 to 1.60; 55 trials) for gum, 1.64 (95% CI 1.52 to 1.78; 43 trials ) for patches, 2.02 (95% CI 1.49 to 2.73; 4 trials) for nasal spray, 1.90 (95% CI: 1.36 to 2.67; 4 trials) for inhaled nicotine, 1.95 (95% CI 1.61 to 2.36; 6 trials) for nicotine sublingual tablet/lozenge, and 2.48 (95% CI 1.24 to 4.94; 1 trial) for oral spray. These RRs were largely independent of additional support provided, duration of treatment or the setting in which the NRT was offered. Eight weeks of patch therapy was as effective as longer courses and there was no evidence that tapered therapy was better than abrupt withdrawal. 4 mg gum was superior to 2 mg gum in highly dependent smokers (RR 1.43, 95% CI 1.12 to 1.83). Combining a nicotine patch with a rapid delivery form of NRT was more effective than a single type of NRT (RR 1.34, 95% CI 1.18 to 1.51; 9 trials). Five studies directly compared NRT to bupropion, and there was no evidence of a difference in efficacy (RR 1.01, 95% CI 0.87 to 1.18).
Another Cochrane review included a network meta-analysis of 12 treatment-specific reviews (267 studies) involving 101804 participants. NRT was superior to placebo (odds ratios (OR) 1.84; 95% credible interval (CredI) 1.71 to 1.99, 119 trials). Head-to-head comparisons between bupropion and NRT showed equal efficacy (OR 0.99; 95% CredI 0.86 to 1.13, 9 trials). Varenicline was superior to single forms of NRT (OR 1.57; 95% CredI 1.29 to 1.91; indirect comparison). Varenicline was more effective than nicotine patch (OR 1.51; 95% CredI 1.22 to 1.87; indirect comparison), than nicotine gum (OR 1.72; 95% CredI 1.38 to 2.13; indirect comparison), and than 'other' NRT (inhaler, spray, tablets, lozenges; OR 1.42; 95% CredI 1.12 to 1.79; indirect comparison), but was not more effective than combination NRT (OR 1.06; 95% CredI 0.75 to 1.48; indirect comparison). Combination NRT also outperformed single formulations. The four categories of NRT performed similarly against each other, apart from 'other' NRT, which was marginally more effective than NRT gum (OR 1.21; 95% CredI 1.01 to 1.46). Mecamylamine in combination with NRT may increase the chances of quitting, but the current evidence is inconclusive.