Ray, Kausik KDel Prato, StefanoMüller-Wieland, DirkCariou, BertrandColhoun, Helen MTinahones, Francisco JDomenger, CatherineLetierce, AlexiaMandel, JonasSamuel, RitaBujas-Bobanovic, MajaLeiter, Lawrence A2023-02-082023-02-082019-11-09http://hdl.handle.net/10668/14662Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin  This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C  Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/AlirocumabAtherosclerotic cardiovascular diseaseDyslipidemiaLow-density lipoprotein cholesterolType 2 diabetes mellitusAntibodies, Monoclonal, HumanizedAnticholesteremic AgentsAtherosclerosisBiomarkersCholesterol, HDLCholesterol, LDLClinical Trials, Phase III as TopicClinical Trials, Phase IV as TopicCoronary DiseaseDiabetes Mellitus, Type 2Drug Therapy, CombinationDyslipidemiasHumansHydroxymethylglutaryl-CoA Reductase InhibitorsMulticenter Studies as TopicPCSK9 InhibitorsRandomized Controlled Trials as TopicRisk FactorsSerine Proteinase InhibitorsTime FactorsTreatment Outcomeresearch article31706300open access10.1186/s12933-019-0951-91475-2840PMC6842201https://doi.org/10.1186/s12933-019-0951-9https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6842201/pdf