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

Aim To examine the lipid and glycaemic effects of 52 weeks of evolocumabtreatment. Materials and Methods DESCARTES was a 52-week placebo-controlled trial of evolocumab. DESCARTES randomised 905 patients from 88 study centres in nine 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 placebowas administered. The main outcomes measured were percentage change in LDL-cholesterol (LDL-C) at week 52 and safety. Results 413 patients had dysglycaemia (120 type 2 diabetes, 293 IFG), 289 MetS (194 also had IFG), and 393 none of these conditions. At week 52, evolocumabreduced LDL-C by > 50% in all subgroups, with favourable effects on other lipids. No significant differences in fasting plasma glucose, HbA1c, insulin, C-peptideor HOMA indices were seen in any subgroup between evolocumaband placeboat 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 Evolocumabshowed 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. NCT01516879, ClinicalTrials.gov