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AIMS: To compare biomarkers of potential harm between people switching from smoking combustible cigarettes (CC) completely to electronic cigarettes (EC); continuing to smoke CC; using both EC and CC (dual users); and using neither (abstainers), based on behaviour during EC intervention studies. DESIGN: Secondary analysis following systematic review, incorporating inverse variance random effects meta-analysis and effect direction plots. SETTING: Greece, Italy, Poland, UK, and USA PARTICIPANTS: 1,299 adults smoking CC (9 studies) and provided EC MEASUREMENTS: Carbon monoxide (CO) and 26 other biomarkers FINDINGS: In pooled analyses, exhaled CO (eCO) was lower in EC versus EC+CC (mean difference (MD) -4.40ppm, 95% confidence interval [CI] -12.04-3.24, 2 studies) and CC (MD -9.57ppm, 95% CI -17.30 to -1.83, 3 studies). eCO was lower in dual users versus CC only (MD -1.91ppm, 95% CI -3.38 to -0.45, 2 studies). Magnitude rather than direction of effect drove substantial statistical heterogeneity. Effect-direction plots were used for other biomarkers. Comparing EC with CC, 12 of 13 biomarkers were significantly lower in EC users, with no difference for the 13th . Comparing EC with dual users, 12 of the 25 biomarkers were lower for EC , and five were lower for dual use. For the remaining eight measures, single studies did not detect statistically significant differences, or the multiple studies contributing to the outcome had inconsistent results. Only one study provided data comparing dual use with CC; of the 13 biomarkers measured, 12 were significantly lower in the dual use group, with no statistically significant difference detected for the 13th. Only one study provided data on abstainers. CONCLUSIONS: Switching from smoking to vaping or dual use appears to reduce levels of biomarkers of potential harm significantly.

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