Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies.

Publisher: BioMed Central Country of Publication: England NLM ID: 101147637 Publication Model: Electronic Cited Medium: Internet ISSN: 1475-2840 (Electronic) Linking ISSN: 14752840 NLM ISO Abbreviation: Cardiovasc Diabetol Subsets: MEDLINE

Original Publication: London : BioMed Central, [2002-

Antibodies, Monoclonal, Humanized/*therapeutic use ; Anticholesteremic Agents/*therapeutic use ; Atherosclerosis/*drug therapy ; Cholesterol, HDL/*blood ; Cholesterol, LDL/*blood ; Coronary Disease/*drug therapy ; Diabetes Mellitus, Type 2/*drug therapy ; Dyslipidemias/*drug therapy ; Serine Proteinase Inhibitors/*therapeutic use; Antibodies, Monoclonal, Humanized/adverse effects ; Anticholesteremic Agents/adverse effects ; Atherosclerosis/blood ; Atherosclerosis/diagnosis ; Atherosclerosis/epidemiology ; Biomarkers/blood ; Clinical Trials, Phase III as Topic ; Clinical Trials, Phase IV as Topic ; Coronary Disease/blood ; Coronary Disease/diagnosis ; Coronary Disease/epidemiology ; Diabetes Mellitus, Type 2/blood ; Diabetes Mellitus, Type 2/diagnosis ; Diabetes Mellitus, Type 2/epidemiology ; Drug Therapy, Combination ; Dyslipidemias/blood ; Dyslipidemias/diagnosis ; Dyslipidemias/epidemiology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use ; Multicenter Studies as Topic ; PCSK9 Inhibitors ; Randomized Controlled Trials as Topic ; Risk Factors ; Serine Proteinase Inhibitors/adverse effects ; Time Factors ; Treatment Outcome

Background: Individuals 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).
Methods: 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 < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies.
Results: 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 < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls.
Conclusions: 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.

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Keywords: Alirocumab; Atherosclerotic cardiovascular disease; Dyslipidemia; Low-density lipoprotein cholesterol; Type 2 diabetes mellitus

ClinicalTrials.gov NCT02642159; NCT02585778

0 (Antibodies, Monoclonal, Humanized)
0 (Anticholesteremic Agents)
0 (Biomarkers)
0 (Cholesterol, HDL)
0 (Cholesterol, LDL)
0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
0 (PCSK9 Inhibitors)
0 (Serine Proteinase Inhibitors)
EC 3.4.21.- (PCSK9 protein, human)
PP0SHH6V16 (alirocumab)

Date Created: 20191111 Date Completed: 20200526 Latest Revision: 20240721

20240721

PMC6842201

10.1186/s12933-019-0951-9

31706300