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Clinical Trial
. 2018 Jun;20(6):1479-1489.
doi: 10.1111/dom.13257. Epub 2018 Mar 23.

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

Kausik K Ray  1 , Lawrence A Leiter  2 , Dirk Müller-Wieland  3 , Bertrand Cariou  4 , Helen M Colhoun  5 , Robert R Henry  6 , Francisco J Tinahones  7 , Maja Bujas-Bobanovic  8 , Catherine Domenger  9 , Alexia Letierce  10 , Rita Samuel  11 , Stefano Del Prato  12
Affiliations
Clinical Trial

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

Kausik K Ray et al. Diabetes Obes Metab. 2018 Jun.

Abstract

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.

Keywords: PCSK9; mixed dyslipidaemia; non-HDL cholesterol; type 2 diabetes.

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Conflict of interest statement

K.K.R. has received: personal fees (data safety monitoring board) from AbbVie, Inc.; consultant fees/honoraria from Aegerion, Algorithm, Amgen, AstraZeneca, Boehringer Ingelheim, Cerenis, Eli Lilly and Company, Ionis Pharmaceuticals, Kowa, Medicines Company, MSD, Novartis, Pfizer, Inc., Regeneron Pharmaceuticals, Inc., Resverlogix, Sanofi and Takeda; and research grants from Kowa, Pfizer, Inc., and Regeneron Pharmaceuticals, Inc. L.A.L. has received: personal fees from Esperion; grants and personal fees from Amgen, AstraZeneca, Eli Lilly and Company, Merck, Regeneron Pharmaceuticals, Inc. and Sanofi; and grants from Kowa and the Medicine Company. D.M.‐W. has received speaker's bureau and consultant/advisory board fees from Amgen, AstraZeneca, Boehringer Ingelheim, MSD (Merck), Novartis, Novo Nordisk and Sanofi. B.C. has received: research funding and personal fees from Sanofi and Regeneron Pharmaceuticals, Inc. during the conduct of the study; research funding from Pfizer, Inc.; and honoraria from AstraZeneca, Pierre Fabre, Janssen, Eli Lilly and Company, MSD Merck & Co., Novo Nordisk, Sanofi and Takeda. H.M.C. has received grants, personal fees and non‐financial support from Sanofi and Regeneron Pharmaceuticals, Inc. during the conduct of the study; grants, personal fees and non‐financial support from Eli Lilly and Company; grants and other support from Roche Pharmaceuticals; grants from Pfizer, Inc., Boehringer Ingelheim, and AstraZeneca LP; and other support from Bayer. R.R.H. has received research funding from AstaMed, Eli Lilly and Company, Hitachi, Lexicon, Novo Nordisk and Viacyte and is a consultant for and/or advisory panel member of Alere, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol‐Myers Squibb, Elcelyx, Gilead, Intarcia, Ionis, Janssen/Johnson & Johnson, Merck and Sanofi‐Aventis. F.J.T. has received speaker's bureau and consultant/advisory board fees from AstraZeneca, Amgen, Boehringer Ingelheim, Bristol‐Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceuticals, Merck Sharpe & Dohme, Novartis Pharmaceuticals Co., Novo Nordisk, Sanofi and Regeneron Pharmaceuticals, Inc. C.D., M.B.‐B. and A.L. are employees of and shareholders in Sanofi. R.S. is an employee of and shareholder in Regeneron Pharmaceuticals, Inc. S.D.P. has received research funding from AstraZeneca, Boheringer Ingelheim, Novartis Pharmaceuticals Co. and Merck Sharpe & Dohme; and is a consultant for or has received honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Janssen Pharmaceuticals, Laboratoires Servier, Merck Sharpe & Dohme, Novartis Pharmaceuticals Co., Novo Nordisk, Sanofi, Servier and Takeda Pharmaceuticals.

Figures

Figure 1
Figure 1
Disposition of individuals for the DM‐DYSLIPIDEMIA study. Abbreviations: ALI, alirocumab; FA, fatty acids; ITT, intention‐to‐treat; LLT, lipid‐lowering therapy; Q2W, every 2 weeks. aThirty‐nine individuals were intended for “no LLT” prior to randomization; however, 37 actually received “no LLT.” One individual intended for “no LLT” received fenofibrate and another received ezetimibe. In total, 4 individuals were not included in the ITT analysis (no non‐HDL cholesterol value available within 1 of the analysis windows up to week 24) and 1 individual was not included in the safety analysis (individual did not wish to continue prior to treatment)
Figure 2
Figure 2
Primary and selected key secondary efficacy endpoints at week 24 for A, the overall study population; B, fenofibrate; C, ezetimibe; D, omega‐3 fatty acids and E, no lipid‐lowering therapy (ITT analysis). Abbreviations: Apo, apolipoprotein; FA, fatty acids; HDL‐C, HDL cholesterol; ITT, intenttion‐to‐treat; LDL‐C, LDL cholesterol; LDL‐P, LDL particle; LLT, lipid‐lowering therapy; Lp(a), lipoprotein (a); LS, least‐squares; TC, total cholesterol; TG, triglyceride. aStatistically significant according to the fixed hierarchical approach used to ensure a strong control of the overall type I error rate at the 0.025 level. ITT analysis includes individuals according to planned treatment (see footnote to Figure 1)
Figure 3
Figure 3
Proportion of individuals achieving predefined lipid goals at A, week 24 and B, week 12 (intention‐to‐treat analysis; as‐planned study cohorts). Abbreviations: ALI, alirocumab; Apo, apolipoprotein; FA, fatty acids; LDL‐C, LDL cholesterol; LLT, lipid‐lowering therapy; non‐HDL‐C, non‐HDL cholesterol; UC, usual care. *P < .05; **P < .0001 vs control. Non‐HDL cholesterol: 2.6 mmol/L = 100 mg/dL; LDL cholesterol: 1.8 mmol/L = 70 mg/dL; ApoB: 0.8 g/L = 80 mg/dL
Figure 4
Figure 4
Percent change from baseline to A, week 12 and B, week 24 in levels of free and total PCSK9 in individuals receiving alirocumab vs usual care (PCSK9 analysis). Abbreviations: ALI, alirocumab; FA, fatty acids; LLT, lipid‐lowering therapy; LS, least squares; PCSK9, proprotein convertase subtilisin‐kexin type 9; UC, usual care
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References

    1. American Diabetes Association . 9. Cardiovascular disease and risk management. Diabetes Care. 2017;40:S75‐S87. - PubMed
    1. Vergès B. Pathophysiology of diabetic dyslipidaemia: where are we? Diabetologia. 2015;58:886‐899. - PMC - PubMed
    1. Ryden L, Grant PJ, Anker SD, et al. ESC guidelines on diabetes, pre‐diabetes, and cardiovascular diseases developed in collaboration with the EASD: the task force on diabetes, pre‐diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and developed in collaboration with the European Association for the Study of Diabetes (EASD). Eur Heart J. 2013;34:3035‐3087. - PubMed
    1. Bays HE, Jones PH, Orringer CE, Brown WV, Jacobson TA. National lipid association annual summary of clinical lipidology 2016. J Clin Lipidol. 2016;10:S1‐43. - PubMed
    1. Catapano AL, Graham I, De Backer G, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37:2999‐3058. - PubMed

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