© 2017 Article author(s) (or their employer(s) unless otherwise stated in the text of the article). All rights reserved. No commercial use is permitted unless otherwise expressly granted. Objective Explore the cost-effectiveness of lifestyle interventions and metformin in reducing subsequent incidence of type 2 diabetes, both alone and in combination with a screening programme to identify high-risk individuals. Design Systematic review of economic evaluations. Data sources and eligibility criteria Database searches (Embase, Medline, PreMedline, NHS EED) and citation tracking identified economic evaluations of lifestyle interventions or metformin alone or in combination with screening programmes in people at high risk of developing diabetes. The International Society for Pharmaco-economics and Outcomes Research's Questionnaire to Assess Relevance and Credibility of Modelling Studies for Informing Healthcare Decision Making was used to assess study quality. Results 27 studies were included; all had evaluated lifestyle interventions and 12 also evaluated metformin. Primary studies exhibited considerable heterogeneity in definitions of pre-diabetes and intensity and duration of lifestyle programmes. Lifestyle programmes and metformin appeared to be cost effective in preventing diabetes in high-risk individuals (median incremental cost-effectiveness ratios of £7490/quality-adjusted life-year (QALY) and £8428/QALY, respectively) but economic estimates varied widely between studies. Intervention-only programmes were in general more cost effective than programmes that also included a screening component. The longer the period evaluated, the more cost-effective interventions appeared. In the few studies that evaluated other economic considerations, budget impact of prevention programmes was moderate (0.13%-0.2% of total healthcare budget), financial payoffs were delayed (by 9-14 years) and impact on incident cases of diabetes was limited (0.1%-1.6% reduction). There was insufficient evidence to answer the question of (1) whether lifestyle programmes are more cost effective than metformin or (2) whether low-intensity lifestyle interventions are more cost effective than the more intensive lifestyle programmes that were tested in trials. Conclusions The economics of preventing diabetes are complex. There is some evidence that diabetes prevention programmes are cost effective, but the evidence base to date provides few clear answers regarding design of prevention programmes because of differences in denominator populations, definitions, interventions and modelling assumptions.