Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome.
To examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab.



The Durable Effect of PCSK9 Antibody Compared with Placebo Study (DESCARTES) was a 52-week placebo-controlled trial of evolocumab that randomized 905 patients from 88 study centres in 9 countries, with 901 receiving at least one dose of study drug. For this post-hoc analysis, DESCARTES patients were categorized by baseline glycaemic status: type 2 diabetes, impaired fasting glucose (IFG), metabolic syndrome (MetS) or none of these. Monthly subcutaneous evolocumab (420 mg) or placebo was administered. The main outcomes measured were percentage change in LDL-cholesterol (LDL-C) at week 52 and safety.



A total of 413 patients had dysglycaemia (120, type 2 diabetes; 293, IFG), 289 had MetS (194 also had IFG) and 393 had none of these conditions. At week 52, evolocumab reduced LDL-C by >50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C-peptide or HOMA indices were seen in any subgroup between evolocumab and placebo at week 52. The overall incidence of new-onset diabetes mellitus did not differ between placebo (6.6%) and evolocumab (5.6%); in those with baseline normoglycaemia, the incidences were 1.9% and 2.7%, respectively. Incidences of AEs were similar in evolocumab- and placebo-treated patients.



Evolocumab showed encouraging safety and efficacy at 52 weeks in patients with or without dysglycaemia or MetS. Changes in glycaemic parameters did not differ between evolocumab- and placebo-treated patients within the glycaemic subgroups examined.
Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa.
Dirk J
DJ
Blom
Jacksonville Center for Clinical Research, Jacksonville, Florida.
Michael J
MJ
Koren
Sterling Research Group, Cincinnati, Ohio.
Eli
E
Roth
Amgen Inc., Thousand Oaks, California.
Maria Laura
ML
Monsalvo
Gilead Sciences, Fremont, California.
C Stephen
CS
Djedjos
Ionis Pharmaceuticals, San Diego, California.
Patric
P
Nelson
Amgen Limited, Cambridge, UK.
Mary
M
Elliott
Amgen Inc., Thousand Oaks, California.
Scott M
SM
Wasserman
Baylor College of Medicine, Houston, Texas.|Houston Methodist DeBakey Heart and Vascular Center, Houston, Texas.
Christie M
CM
Ballantyne
Diabetes Trials Unit, OCDEM, University of Oxford, Oxford, UK.
Rury R
RR
Holman
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D002096:C-Peptide / Q000378:metabolism; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D018149:Glucose Intolerance / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000453:epidemiology / Q000378:metabolism*; D008875:Middle Aged; D016896:Treatment Outcome; D014280:Triglycerides / Q000378:metabolism
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000924:Anticholesteremic Agents; D001786:Blood Glucose; D002096:C-Peptide; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006442:Glycated Hemoglobin; D007328:Insulin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human; C577155:evolocumab
disease; dyslipidaemia; lipid-lowering therapy; macrovascular; phase III study