Randomised study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Primary results of the BERSON clinical trial

Diabetes Obes Metab. 2019 Jun;21(6):1455-1463. doi: 10.1111/dom.13680. Epub 2019 Apr 2.

Abstract

Aim: To evaluate the lipid-lowering efficacy and safety of evolocumab combined with background atorvastatin in patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia.

Materials and methods: BERSON was a double-blind, 12-week, phase 3 study (NCT02662569) conducted in 10 countries. Patients ≥18 to ≤80 years with type T2DM received atorvastatin 20 mg/d and were randomised 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Co-primary endpoints were the percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures, and adverse events (AEs).

Results: Overall, 981 patients were randomised and received ≥1 dose of study drug. Evolocumab significantly reduced LDL-C versus placebo at week 12 (Q2W, -71.8%; QM, -74.9%) and at the mean of weeks 10 and 12 (Q2W, -70.3%; QM, -70.0%; adjusted P < 0.0001 for all) when administered with atorvastatin. Non-high-density lipoprotein cholesterol, apolipoprotein B100, total cholesterol, lipoprotein (a), triglycerides, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol improved significantly with evolocumab versus placebo. The overall incidence of AEs was similar between evolocumab and placebo-treated patients, and there were no clinically meaningful differences in changes over time in glycaemic variables (fasting serum glucose and HbA1c) between the two groups.

Conclusions: In patients with T2DM and hyperlipidaemia or mixed dyslipidaemia on statin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Keywords: dyslipidaemia; evolocumab; hyperlipidaemia; phase 3; type 2 diabetes.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Anticholesteremic Agents / adverse effects
  • Anticholesteremic Agents / pharmacology
  • Anticholesteremic Agents / therapeutic use*
  • Blood Glucose / drug effects
  • Cholesterol / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Dyslipidemias* / complications
  • Dyslipidemias* / drug therapy
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Male
  • Middle Aged

Substances

  • Antibodies, Monoclonal, Humanized
  • Anticholesteremic Agents
  • Blood Glucose
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Cholesterol
  • evolocumab