Treatment with evolocumab as an add-on to statin therapy in patients with type 2 diabetes (T2D) led to a significant reduction in low-density lipoprotein cholesterol (LDL-C) concentrations. Furthermore, evolocumab combined with moderate intensity atorvastatin was well tolerated and safe, according to study results published in Diabetes, Obesity and Metabolism.
Statins are the first-line therapy for LDL-C reduction, but previous studies have reported evolocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9, reduced LDL-C when given in combination with a statin alone or in combination with lipid-lowering treatment.
In the BERSON study (evolocumaB Efficacy for LDL-C Reduction in subjects with T2DM On background statiN), the investigators assessed the efficacy and safety of evolocumab with atorvastatin in patients with T2D and hyperlipidemia or mixed dyslipidemia.
BERSON was a 12-week, randomized, double-blind, placebo-controlled, phase 3 study that included 98 centers in 10 countries; one-half of the patients were from China. The investigators assessed the efficacy of subcutaneous evolocumab once every 2 weeks or once a month combined with atorvastatin 20 mg/d vs placebo. The primary outcome was the percentage change in LDL-C levels from baseline.
The study enrolled adult patients (age ≥18 to ≤80) with T2D. All patients receiving statins at screening were required to have an LDL-C level ≥100 mg/dL; patients not receiving statin therapy were required to have an LDL-C level ≥130 mg/dL. The participants were randomly assigned on a 2:2:1:1 basis to evolocumab 140 mg every 2 weeks or 420 mg every month, or placebo every 2 weeks or once a month.
Of the 2494 patients screened, 981 (57% women; mean age, 61.3 years; 50% Asian) received ≥1 dose of the study medication.
Compared with placebo, treatment with evolocumab significantly reduced LDL-C at week 12 (least squares mean), both with dosing every 2 weeks (-71.8% ± 3%; 95% CI, -77.6 to -65.9; P <.0001) and once a month (-64.9%; 95% CI, -70.0 to -59.9; P <.0001). Furthermore, at week 12, LDL-C concentrations were reduced to <70 mg/dL in 88% of patients treated with evolocumab every 2 weeks and in 90% of patients treated monthly.
Treatment with evolocumab was also associated with significant improvement in other lipid parameters, including non-high-density lipoprotein cholesterol, apolipoprotein B100, triglycerides, lipoprotein(a), and high-density lipoprotein cholesterol.
The combination of evolocumab with atorvastatin in this study was well tolerated, and the overall incidence of adverse events (AEs) was similar with evolocumab and placebo (43.8% vs 42.6%, respectively). Most AEs were grade 1 or 2. Exacerbation or worsening of preexisting diabetes, upper respiratory tract infection, and hypertension were the most common AEs with evolocumab.
Most diabetes-related AEs were mild and did not require discontinuation of evolocumab in any patient. There were no clinically meaningful differences in fasting plasma glucose or glycated hemoglobin in either treatment group during the study.
Study limitations included the short duration, small sample size, and use of nonintensive statin treatment.
In patients with T2D with hyperlipidemia or mixed dyslipidemia, “evolocumab on background atorvastatin significantly reduced LDL-C, [and] allowed the vast majority of patients to achieve LDL-C levels below 1.8 mmol/L,” concluded the researchers. In addition, they stressed that evolocumab was safe and well tolerated, with a notable effect on measures of glycemic control.
This study was funded by Amgen Inc.
Lorenzatti AJ, Eliaschewitz FG, Chen Y, et al. Randomized study of evolocumab in patients with type 2 diabetes and dyslipidemia on background statin: primary results of the BERSON clinical trial [published online March 1, 2019]. Diabetes Obes Metab. doi:10.1111/dom.13680