Alirocumab versus 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

AIMS: Individuals with type 2 diabetes (T2DM) and mixed dyslipidaemia represent a high-risk and difficult-to-treat population. ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) compared alirocumab, a proprotein convertase subtilisin-kexin type 9 inhibitor, with usual care (UC) in individuals with T2DM and mixed dyslipidaemia not optimally managed by maximally-tolerated statins.

MATERIALS AND METHODS: 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 (Q2W; with increase to 150 mg Q2W at Week [W]12 if W8 non-high-density lipoprotein cholesterol [non-HDL-C] was ≥2.59 mmol/L [100 mg/dL]) or UC for 24 weeks. Primary efficacy endpoint was percentage change in non-HDL-C from baseline to W24.

RESULTS: The randomized population comprised 413 individuals (409 intention-to-treat; 412 safety). At W24, mean non-HDL-C 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 Q2W. Alirocumab also reduced low-density lipoprotein cholesterol (-43.0%), apolipoprotein B (-32.3%), total cholesterol (-24.6%), and LDL particle number (-37.8%) at W24 vs UC (all P<.0001). Consistent with the overall trial comparison, alirocumab reduced non-HDL-C to a greater degree within each UC stratum at W24. Incidence of treatment-emergent adverse events was 68.4% (alirocumab) and 66.4% (UC). No clinically meaningful effect on glycated hemoglobin, 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 in non-HDL-C reduction vs UC and was generally well tolerated.