Background: REDUCE-IT, a multinational, double-blind trial, randomized 8179 statin-treated patients with controlled low density lipoprotein cholesterol, elevated triglycerides, and cardiovascular (CV) risk, to icosapent ethyl (IPE) 4 grams daily or placebo. IPE reduced the primary (CV death, myocardial infarction MI, stroke, coronary revascularization, hospitalization for unstable angina) and key secondary (CV death, MI, stroke) endpoints 25% and 26%, respectively (each p<0.000001). At baseline, median body mass index (BMI) was 30.8 kg/m2, and 58.5% of REDUCE-IT patients had diabetes mellitus (DM). In patients with DM, the primary and key secondary endpoints were reduced 23% and 30%, respectively (each p≤0.00005). Methods: We evaluated if BMI modulated CV risk reduction with IPE in patients with or without DM. Results: In the full cohort, similar CV risk reduction was observed across the prespecified endpoint testing hierarchy (interaction p=ns for all), and relative safety between treatment groups was generally consistent. In persons with or without DM, similar reductions in the primary endpoint were observed across BMI categories (Figure), with similar findings in the key secondary endpoint (interaction p=ns for all). Conclusion: The significant cardiovascular risk reduction provided by IPE 4g/day is consistent across BMI in patients with and without DM.