Alirocumab vs usual lipid-lowering care as add-on to statin therapy in individuals with type 2 diabetes and mixed dyslipidaemia: The ODYSSEY DM-DYSLIPIDEMIA randomized trial.

AIM: To compare alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia not optimally managed by maximally tolerated statins in the ODYSSEY DM-DYSLIPIDEMIA trial (NCT02642159). MATERIALS AND METHODS The UC options (no additional lipid-lowering therapy; fenofibrate; ezetimibe; omega-3 fatty acid; nicotinic acid) were selected prior to stratified randomization to open-label alirocumab 75 mg every 2 weeks (with increase to 150 mg every 2 weeks at week 12 if week 8 non-HDL cholesterol concentration was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. The primary efficacy endpoint was percentage change in non-HDL cholesterol from baseline to week 24. RESULTS The randomized population comprised 413 individuals (intention-to-treat population, n = 409; safety population, n = 412). At week 24, the mean non-HDL cholesterol reductions were superior with alirocumab (-32.5% difference vs UC, 97.5% confidence interval -38.1 to -27.0; P < .0001). Overall, 63.6% of alirocumab-treated individuals were maintained on 75 mg every 2 weeks. Alirocumab also reduced LDL cholesterol (-43.0%), apolipoprotein B (-32.3%), total cholesterol (-24.6%) and LDL particle number (-37.8%) at week 24 vs UC (all P < .0001). Consistent with the overall trial comparison, alirocumab reduced non-HDL cholesterol to a greater degree within each UC stratum at week 24. The incidence of treatment-emergent adverse events was 68.4% (alirocumab) and 66.4% (UC). No clinically meaningful effect on glycated haemoglobin, or change in number of glucose-lowering agents, was seen. CONCLUSIONS In individuals with T2DM and mixed dyslipidaemia on maximally tolerated statin, alirocumab showed superiority to UC in non-HDL cholesterol reduction and was generally well tolerated.