Evaluation of the efficacy, safety and glycaemic effects of evolocumab (AMG 145) in hypercholesterolaemic patients stratified by glycaemic status and metabolic syndrome

Diabetes Obes Metab. 2017 Jan;19(1):98-107. doi: 10.1111/dom.12788. Epub 2016 Oct 14.


Aim: To examine the lipid and glycaemic effects of 52 weeks of treatment with evolocumab.

Materials and methods: 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.

Results: 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.

Conclusions: 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.

Trial registration: ClinicalTrials.gov NCT01516879.

Keywords: disease; dyslipidaemia; lipid-lowering therapy; macrovascular; phase III study.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents / therapeutic use*
  • Blood Glucose / metabolism
  • C-Peptide / metabolism
  • Case-Control Studies
  • Cholesterol, HDL / metabolism
  • Cholesterol, LDL / metabolism
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / metabolism*
  • Female
  • Glucose Intolerance / complications
  • Glucose Intolerance / epidemiology
  • Glucose Intolerance / metabolism*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypercholesterolemia / complications
  • Hypercholesterolemia / drug therapy*
  • Hypercholesterolemia / metabolism
  • Insulin / metabolism
  • Insulin Resistance
  • Male
  • Metabolic Syndrome / complications
  • Metabolic Syndrome / epidemiology
  • Metabolic Syndrome / metabolism*
  • Middle Aged
  • Treatment Outcome
  • Triglycerides / metabolism


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Blood Glucose
  • C-Peptide
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Insulin
  • Triglycerides
  • hemoglobin A1c protein, human
  • evolocumab

Associated data

  • ClinicalTrials.gov/NCT01516879