Post-Cessation Weight Gain Across Smoking Cessation Therapies: A Review of Secondary Analyses from the ZESCA, EVITA, and E3 Trials

<b>Background:</b> Post-cessation weight gain is a barrier to smoking abstinence, yet evidence on the role of e-cigarettes in mitigating this remains limited. <b>Objective:</b> To examine weight-related effects of e-cigarettes in comparison with established cessation methods. <b>Methods:</b> We reviewed data from three cessation trials we conducted between 2005 and 2020. In ZESCA and EVITA, patients were randomized to bupropion or varenicline versus placebo. In the E3 trial, participants were randomized to counseling alone or with nicotine or non-nicotine e-cigarettes. Post hoc analyses assessed weight at 52 weeks for bupropion and varenicline, and 12 weeks for e-cigarettes. <b>Synthesis:</b> Abstinent individuals showed significant weight gain from baseline across the trials. In ZESCA and EVITA, abstinent participants gained more weight than intermittent and persistent smokers at 52 weeks (ZESCA: 4.8 vs. 2.0 vs. 3.0 kg, EVITA: 4.8 vs. 2.0 vs. -0.7 kg, respectively). Abstinent individuals gained more weight than persistent smokers (ZESCA: 3.4 kg, EVITA: 5.5 kg). In the E3 trial, abstinent participants with nicotine e-cigarettes gained more weight than those using non-nicotine e-cigarettes or counseling at 12 weeks (2.7 vs. 2.3 vs. 2.1 kg, respectively). <b>Conclusions:</b> Abstinent individuals experienced significant weight gain regardless of cessation treatment. Long-term effects of e-cigarettes on weight remain unclear.