The Journal of Clinical Endocrinology and Metabolism Journal Article

Efficacy and Safety of Alirocumab 300 mg Every 4 Weeks in Individuals With Type 2 Diabetes on Maximally Tolerated Statin

June 05, 2019

Dirk Müller-Wieland, Daniel J Rader, Patrick M Moriarty, Jean Bergeron, Gisle Langslet, Kausik K Ray, Garen Manvelian, Desmond Thompson, Maja Bujas-Bobanovic, Eli M Roth
The Journal of Clinical Endocrinology & Metabolism, Volume 104, Issue 11, November 2019, Pages 5253–5262
https://doi.org/10.1210/jc.2018-02703

Abstract

Context

In the ODYSSEY CHOICE I trial, alirocumab 300 mg every 4 weeks (Q4W) was assessed in patients with hypercholesterolemia. Alirocumab efficacy and safety were evaluated in a patient subgroup with type 2 diabetes mellitus (T2DM) and who were receiving maximally tolerated statins with or without other lipid-lowering therapies.

Methods

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 every 2 weeks at Week (W) 12 if W8 low-density lipoprotein cholesterol (LDL-C) levels were ≥70 mg/dL or ≥ 100 mg/dL, depending on cardiovascular risk, or if LDL-C reduction was <30% from baseline. Efficacy end points included percentage change from baseline to W24 for lipids, and time-averaged LDL-C over W21 to W24.

Design

A randomized, placebo-controlled trial in children 8 to 17 years of age with T1D using placebo or prebiotic oligofructose-enriched inulin for 12 weeks. Baseline, 3-month, and 6-month assessments included HbA1c, C-peptide, gut microbiota, intestinal permeability, frequency of diabetic ketoacidosis (DKA), and severe hypoglycemia.

Results

In individuals with T2DM, LDL-C reductions from baseline to W24 and the average of W21 to W24 were significantly greater with alirocumab (−61.6% and −68.8%, respectively) vs placebo. At W24, alirocumab significantly reduced levels of non–high-density lipoprotein cholesterol (HDL-C) and other lipids. At W24, 85.9% and 12.5% of individuals in the alirocumab and placebo groups, respectively, reached both non–HDL-C <100 mg/dL and LDL-C <70 mg/dL. At W12, In total, 18% of alirocumab-treated participants received dose adjustment. The 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.

Conclusion

In individuals with T2DM, alirocumab 300 mg Q4W was generally well tolerated and efficacious in reducing atherogenic lipoproteins.

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