PMID- 32035487
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20211204
IS  - 1475-2840 (Electronic)
IS  - 1475-2840 (Linking)
VI  - 19
IP  - 1
DP  - 2020 Feb 8
TI  - Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and 
      low high-density lipoprotein cholesterol.
PG  - 14
LID - 10.1186/s12933-020-0991-1 [doi]
LID - 14
AB  - BACKGROUND: Mixed dyslipidemia [elevated non-high-density lipoprotein cholesterol 
      (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 
      diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. 
      Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for 
      mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase 
      subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein 
      cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is 
      well-tolerated in individuals with T2DM. METHODS: The previously reported 
      open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of 
      alirocumab on individuals with non-HDL-C >/= 100 mg/dL and 
      TGs >/= 150 and < 500 mg/dL receiving stable maximally tolerated statin (n = 413). 
      This post hoc subgroup analysis of the primary trial investigated the effects of 
      alirocumab [75 mg every 2 weeks (Q2W) with possible increase to 150 mg Q2W at 
      Week 12] versus usual care [ezetimibe, fenofibrate, or no additional 
      lipid-lowering therapy (LLT)] on non-HDL-C and other lipids in individuals with 
      T2DM and baseline TGs >/= 200 mg/dL and HDL-C < 40 mg/dL (men) or < 50 mg/dL 
      (women). RESULTS: Alirocumab significantly reduced non-HDL-C [LS mean difference 
      (standard error (SE)), - 35.0% (3.9)], ApoB [LS mean difference (SE), - 34.7% 
      (3.6)], LDL-C [LS mean difference (SE), - 47.3% (5.2)], LDL particle number [LS 
      mean difference (SE), - 40.8% (4.1)], and Lp(a) [LS mean difference (SE), - 29.9% 
      (5.4)] versus usual care from baseline to Week 24 (all P < 0.0001). Results were 
      similar for alirocumab versus usual care. TG reductions were similar between 
      alirocumab and usual care (no significant difference), but greater with 
      fenofibrate versus alirocumab (P = 0.3371). Overall, alirocumab significantly 
      increased HDL-C versus usual care [LS mean difference (SE), 7.9% (3.6); 
      P < 0.05], although differences with alirocumab versus ezetimibe or fenofibrate 
      were non-significant. Most individuals receiving alirocumab achieved 
      ApoB < 80 mg/dL (67.9%) and non-HDL-C < 100 mg/dL (60.9%). Adverse event 
      frequency was similar between alirocumab (67.2%) and usual care (70.7%). 
      Additionally, no clinically relevant effect of alirocumab on change in glycemic 
      parameters or use of antihyperglycemic agents was observed. CONCLUSIONS: 
      Alirocumab is an effective therapeutic option for individuals with T2DM, 
      TGs >/= 200 mg/dL, and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women). Atherogenic 
      lipid (ApoB and non-HDL) reductions were greater with alirocumab than ezetimibe, 
      fenofibrate, or no LLT. Consistent with previous studies, alirocumab was 
      generally well tolerated. Trial registration Clinicaltrials.gov, NCT02642159. 
      Registered December 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02642159.
FAU - Colhoun, Helen M
AU  - Colhoun HM
AD  - The Institute of Genetics and Molecular Medicine, University of Edinburgh, 
      Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK. 
      helen.colhoun@igmm.ed.ac.uk.
FAU - Leiter, Lawrence A
AU  - Leiter LA
AD  - Li Ka Shing Knowledge Institute, St. Michael's Hospital, University of Toronto, 
      Toronto, ON, Canada.
FAU - Muller-Wieland, Dirk
AU  - Muller-Wieland D
AD  - Department of Internal Medicine I, University Hospital Aachen, Aachen, Germany.
FAU - Cariou, Bertrand
AU  - Cariou B
AD  - l'institut du thorax, CHU Nantes, INSERM, CNRS, UNIV Nantes, Nantes, France.
FAU - Ray, Kausik K
AU  - Ray KK
AD  - Imperial Centre for Cardiovascular Disease Prevention, Department of Primary Care 
      and Public Health, Imperial College, London, UK.
FAU - Tinahones, Francisco J
AU  - Tinahones FJ
AD  - Department of Clinical Endocrinology and Nutrition (IBIMA), Hospital Virgen de la 
      Victoria, University of Malaga, CIBER Fisiopatologia de la Obesidad y Nutricion 
      (CIBERobn), Instituto de Salud Carlos III, Malaga, Spain.
FAU - Domenger, Catherine
AU  - Domenger C
AD  - Sanofi, Gentilly, France.
FAU - Letierce, Alexia
AU  - Letierce A
AD  - Biostatistics and Programming Department, Sanofi, Chilly-Mazarin, France.
FAU - Israel, Marc
AU  - Israel M
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
FAU - Samuel, Rita
AU  - Samuel R
AD  - Regeneron Pharmaceuticals, Inc, Tarrytown, NY, USA.
FAU - Del Prato, Stefano
AU  - Del Prato S
AD  - Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 
      Italy.
LA  - eng
SI  - ClinicalTrials.gov/NCT02642159
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200208
PL  - England
TA  - Cardiovasc Diabetol
JT  - Cardiovascular diabetology
JID - 101147637
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Anticholesteremic Agents)
RN  - 0 (Biomarkers)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (PCSK9 Inhibitors)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Triglycerides)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - PP0SHH6V16 (alirocumab)
SB  - IM
MH  - Aged
MH  - Antibodies, Monoclonal, Humanized/adverse effects/*therapeutic use
MH  - Anticholesteremic Agents/adverse effects/*therapeutic use
MH  - Biomarkers/blood
MH  - Cholesterol, HDL/*blood
MH  - Diabetes Mellitus, Type 2/blood/diagnosis/*drug therapy
MH  - Dyslipidemias/blood/diagnosis/*drug therapy
MH  - Female
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - *PCSK9 Inhibitors
MH  - Protease Inhibitors/adverse effects/*therapeutic use
MH  - Time Factors
MH  - Treatment Outcome
MH  - Triglycerides/*blood
PMC - PMC7007683
OTO - NOTNLM
OT  - Alirocumab
OT  - DM-DYSLIPIDEMIA
OT  - Diabetes mellitus
OT  - HDL-C
OT  - Non-HDL-C
OT  - ODYSSEY
OT  - PCSK9
OT  - Triglycerides
OT  - Type 2 diabetes
OT  - Usual care
COIS- HMC has received speaker's bureau and consultant/advisory board fees from Sanofi 
      Aventis, Regeneron Pharmaceuticals, Inc., Novartis Pharmaceuticals, Novo-Nordisk, 
      and Eli Lilly; has received non-binding research support from Pfizer Inc., 
      AstraZeneca LP, and Novo-Nordisk; and is a shareholder of Roche Pharmaceuticals 
      and Bayer. LAL has received grants and personal fees from Amgen, AstraZeneca, Eli 
      Lilly and Company, Esperion, HLS, Merck, Regeneron Pharmaceuticals, Inc., and 
      Sanofi; and grants from Kowa and the Medicines Company. DM-W has received 
      consultant fees/honoraria from Amgen Inc., AstraZeneca, Boehringer Ingelheim 
      Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Corporation, Novo Nordisk 
      Inc., and Sanofi-Aventis; and participated in speaker's bureau for Amgen Inc., 
      AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, 
      Merck & Co., Inc., Novartis Corporation, Novo Nordisk Inc., and Sanofi-Aventis. 
      BC has received research funding and personal fees from Sanofi and Regeneron 
      Pharmaceuticals, Inc.; research funding from Amgen and Pfizer; and honoraria from 
      Amgen, Akcea, AstraZeneca, Pierre Fabre, Genfit, Gilead, Eli Lilly and Company, 
      MSD (Merck & Co.), Novo Nordisk, Sanofi, and Servier. KKR has received research 
      grants from Pfizer Inc., Amgen, Sanofi, Regeneron Pharmaceuticals, Inc., and MSD; 
      honoraria from Dr Reddy's Laboratories, Zuellig Pharma, Sanofi, Amgen, Boehringer 
      Ingelheim, Novo Nordisk, and Pfizer Inc.; and consultant/advisory board fees from 
      Medco, AstraZeneca, Resverlogix, Kowa, Abbvie, Sanofi, Amgen, Boehringer 
      Ingelheim, Esperion, Akcea, and Regeneron Pharmaceuticals, Inc. FJT 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, MSD (Merck & Co.), Novartis 
      Pharmaceuticals Co., Novo Nordisk, and Sanofi-Aventis. CD and AL are employees of 
      and stockholders in Sanofi. MKI and RS are employees of and stockholders in 
      Regeneron Pharmaceuticals, Inc. SDP has received research funding from 
      AstraZeneca, Boehringer Ingelheim, Novartis Pharmaceuticals Co., and MSD (Merck & 
      Co.); and has been a consultant for or received honoraria from AstraZeneca, 
      Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Janssen 
      Pharmaceuticals, Laboratoires Servier, MSD (Merck & Co.), Novartis 
      Pharmaceuticals Co., Novo Nordisk, Sanofi-Aventis, and Takeda Pharmaceuticals.
EDAT- 2020/02/10 06:00
MHDA- 2020/09/01 06:00
PMCR- 2020/02/08
CRDT- 2020/02/10 06:00
PHST- 2019/11/07 00:00 [received]
PHST- 2020/01/22 00:00 [accepted]
PHST- 2020/02/10 06:00 [entrez]
PHST- 2020/02/10 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2020/02/08 00:00 [pmc-release]
AID - 10.1186/s12933-020-0991-1 [pii]
AID - 991 [pii]
AID - 10.1186/s12933-020-0991-1 [doi]
PST - epublish
SO  - Cardiovasc Diabetol. 2020 Feb 8;19(1):14. doi: 10.1186/s12933-020-0991-1.