Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre‐specified analysis of the Chinese population from the BERSON clinical trial

Abstract

Aim The aim of this study was to evaluate the efficacy and safety of evolocumab with background atorvastatin in Chinese patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia. Materials and methods This is a pre‐specified analysis of patients in the BERSON study (http://clinicaltrials.gov, NCT02662569) in China. Patients initiated background atorvastatin 20 mg/d, after which they were randomized 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or to placebo Q2W or QM. Co‐primary endpoints were percentage change in LDL 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 Among 453 patients randomized in China, 451 received at least one dose of study drug (evolocumab or placebo). Evolocumab significantly reduced LDL‐C compared with placebo at week 12 (Q2W, −85.0%; QM, −74.8%) and at the mean of weeks 10 and 12 (Q2W, −80.4%; QM, −81.0%) (adjusted P < 0.0001 for all) when administered with background atorvastatin. Non‐HDL‐C, ApoB100, total cholesterol, Lp(a), triglycerides, HDL‐C and VLDL‐C significantly improved with evolocumab vs placebo. No new safety findings were observed with evolocumab. The incidence of diabetes AEs was higher with evolocumab compared with placebo. There were no differences over time between evolocumab and placebo in measures of glycaemic control. Conclusions In patients in China with T2DM and hyperlipidaemia or mixed dyslipidaemia receiving background atorvastatin, evolocumab significantly reduced LDL‐C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

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

“…Approximately 50% of the patients in BERSON were enrolled at centres in China; a prespecified analysis of the efficacy and safety of evolocumab in the China population is reported by Chen at al. 25 2 | METHODS 2.1 | Study design and participants BERSON (ClinicalTrials.gov, NCT02662569) was a 12-week, randomised, double-blind, placebo-controlled, phase 3 study conducted at 98 centres in 10 countries (Argentina, Brazil, Canada, China, Colombia, France, Republic of Korea, Russian Federation, Turkey, and the United States). This global study was designed to recruit one half of its patients from China.…”

Effects of evolocumab therapy and low LDL‐C levels on vitamin E and steroid hormones in Chinese and global patients with type 2 diabetes

“…As previously reported, the BERSON study randomized 324 patients to placebo and 657 to evolocumab (149 and 302, respectively, in China) (Table 1). Overall, the mean age was 61 years, and the proportion of female patients was 57%.…”

“…The design and results of the BERSON study (ClinicalTrials.gov, NCT02662569) have been previously described . Briefly, this was a double‐blind, randomized, placebo‐controlled clinical trial conducted in 10 countries (Argentina, Brazil, Canada, China, Colombia, France, Republic of Korea, Russian Federation, Turkey and the United States).…”

“…Lipid‐lowering therapy status had to be unchanged for ≥4 weeks before LDL‐C screening. Patients on statin therapy at screening with an LDL‐C of ≥2.6 mmol/L and those not on statin therapy at screening with an LDL‐C of ≥3.4 mmol/L entered in a lipid stabilization period and started daily oral atorvastatin 20 mg, after which eligible patients were randomized to subcutaneous evolocumab 140 mg every 2 weeks (Q2W), evolocumab 420 mg monthly (QM), placebo Q2W or placebo QM (2:2:1:1) added to daily oral atorvastatin 20 mg. Dosing groups were pooled in the present analysis of vitamin E and steroidal and gonadal hormones because the doses were clinically equivalent in prior analyses . The co‐primary end‐points of the BERSON study were per cent change in LDL‐C from baseline to week 12 and to the mean of weeks 10 and 12.…”

“…A recently reported clinical trial (BERSON; NCT02662569) confirmed the efficacy of evolocumab in reducing LDL‐C over 12 weeks among patients with type 2 diabetes and hypercholesterolaemia or mixed dyslipidaemia . The BERSON study is the largest diabetes trial with evolocumab performed to date and the first to include a large cohort of patients enrolled in China …”