Lipid-lowering efficacy of the PCSK9 inhibitor evolocumab (AMG 145) in patients with type 2 diabetes: a meta-analysis of individual patient data

Abstract

Background Patients with type 2 diabetes mellitus (T2DM) have elevated cardiovascular risk. PCSK9 monoclonal antibodies have been shown to reduce LDL-C and other lipids, but specific efficacy for patients with diabetes is unknown. Methods We studied the effect of the PCSK9 inhibitor evolocumab on lipid parameters (LDL-C, non-HDL-cholesterol, total cholesterol, triglycerides, lipoprotein(a), HDL-C) in patients with and without T2DM. We searched Medline and EMBASE (2012-2015) to identify 12-week phase 3 trials of subcutaneous evolocumab therapy once every 2 weeks or once monthly versus placebo or ezetimibe. We used random effects meta-analyses to combine data. Subgroups of T2DM patients (by glycaemia, insulin use, renal function and cardiovascular disease status) were also compared. Findings Data were available for 413 patients with, and 2,119 without, T2DM in three trials. After 12 weeks of evolocumab therapy, mean (95% CI) reductions in LDL-C were 60% (51-69%) versus placebo and 39% (32-47%) versus ezetimibe in patients with T2DM. Reductions were 66% (62-70%) and 40% (36-45%), respectively, in patients without T2DM. In patients with T2DM, reductions observed with evolocumab compared with placebo and ezetimibe were 55% (47-63%) and 34% (26-41%) for non-HDL-cholesterol, 38% (32-44%) and 24% (16-31%) for total cholesterol, 31% (25-37%) and 26% (16-35%) for lipoprotein(a), respectively; increases in HDL-C of 8% (4-11%) and 8% (4-13%), respectively, were also observed. Findings across diabetes subgroups were comparable. Interpretation Evolocumab markedly reduces atherogenic lipoproteins in T2DM, an effect consistent across T2DM subgroups, and comparable to changes in patients without T2DM. Cardiovascular outcomes trials are ongoing