BACKGROUND: Individuals with diabetes and elevated LDL-C are at particularly high risk of atherosclerotic cardiovascular disease. ODYSSEY CHOICE I (NCT01926782) assessed alirocumab 300 mg every 4 weeks (Q4W) in patients with hypercholesterolemia. We evaluated alirocumab efficacy and safety in a patient subgroup with type 2 diabetes (T2DM) on maximally tolerated statins with/without other lipid-lowering therapies. METHODS: CHOICE I study participants received either alirocumab 300 mg Q4W (n=458, including 96 with T2DM) or placebo (n=230, including 50 with T2DM) for 48 weeks, with alirocumab dose adjustment to 150 mg Q2W at Week (W)12 if W8 LDL-C levels were ≥70/100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline. Efficacy endpoints included percentage change from baseline to W24 for LDL-C and other lipids, and time-averaged LDL-C over W21-24. RESULTS: In individuals with T2DM, LDL-C reductions from baseline to W24 and average of W21-24 were significantly greater with alirocumab (-61.6% and -68.8% vs placebo, respectively). At W24, alirocumab also significantly reduced levels of non-HDL-C, apolipoprotein B, triglycerides, and lipoprotein (a). At W24, 85.9% (alirocumab) and 12.5% (placebo) of individuals reached both non-HDL-C <100 mg/dL and LDL-C <70 mg/dL. At W12, 18% of alirocumab-treated individuals received dose adjustment. Most common treatment-emergent adverse events were upper respiratory tract infection and injection-site reaction. No clinically significant changes in fasting plasma glucose and glycated hemoglobin were observed. CONCLUSIONS: In individuals with T2DM, alirocumab 300 mg Q4W dosing regimen is generally well tolerated and efficacious in reducing atherogenic lipoproteins represented by LDL-C and non-HDL-C.