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

Abstract

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.