Effects of PCSK9 Inhibition by Evolocumab on Postprandial Lipid Metabolism in Type 2 Diabetes

Marja-Riitta Taskinen

Status and phase

Completed

Phase 4

Conditions

Type 2 Diabetes Mellitus

Treatments

Drug: Evolocumab

Study type

Interventional

Funder types

Other

Identifiers

NCT02948777

EVOLKIN

Details and patient eligibility

About

Postprandial lipemia is highly prevalent in type 2 diabetes subjects even with normal fasting triglyceride values. Humans are mostly in a postprandial rather than in a fasting state and therefore non-fasting triglyceride values reflect more accurately the continuous exposure of arterial wall to the substantial cholesterol load from remnant particles. Evolocumab lowers blood LDL-cholesterol. This study evaluates the effect of evolocumab on postprandial lipid metabolism in type 2 diabetes. All participants in this study receive evolocumab treatment.

Enrollment

14 patients

Sex

All

Ages

18 to 77 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Male or female (non-fertile or using a medically approved birth control method) overweight/obese subjects with Type 2 Diabetes Mellitus treated with lifestyle counselling and a stable metformin dose for at least three months
age 18-77 yrs.
body mass index 25-40 kg/m2
triglycerides between 1.5-4.5 mmol/L and low-density-lipoprotein cholesterol >1.8 but ≤4.0 mmol/L (on Atorvastatin 20 mg/day)
glycohemoglobin: ≤9%.
Each patient will attend a pre-screening visit (at week -5) where eligibility criteria will be evaluated. If the patient uses another statin than atorvastatin (20 mg) at screening visit the used statin is stopped and atorvastatin 20 mg will be initiated. If the patient is not using any statin, atorvastatin 20 mg will be initiated and the lipid values will be checked after 4 weeks when all inclusion/exclusion criteria will be assessed.

Exclusion criteria

Type 1 diabetes
apolipoprotein E2/2 phenotype
alanine transaminase / aspartate transaminase > 3× upper limit of normal
creatinine kinase>3× upper limit of normal
glomerular filtration rate <60 ml/min
clinically significant thyroid-stimulating hormone outside the normal range
body mass index >40 kg/m2
glycohemoglobin > 9.0 %
fasting triglycerides > 4.5 mmol/l
total cholesterol > 7.0 mmol/l
positive urine or serum pregnancy test
untreated or inadequately treated hypertension defined as blood pressure >160 mmHg systolic and/or >105 mmHg diastolic, use of thiazide diuretics at a dose of ≥25 mg/day
subject not on a stable dose of atorvastatin (20 mg/ day before randomization)
lipid-lowering drugs other than statins within 3 months
any other diabetes medication except diet + metformin
history/diagnosis of diabetes nephropathy / retinopathy
current smoking
weekly alcohol use over 24 doses for men and 16 for women
history of myocardial infarction, acute coronary syndrome or coronary revascularization (percutaneous coronary intervention or coronary artery bypass grafting) within the last 6 mos.
planned revascularization (eg coronary artery bypass grafting, percutaneous coronary intervention, carotid or peripheral revascularization procedures) within 3 months of screening
New York Heart Association class III/IV congestive heart failure persisting despite treatment
history of hemorrhagic stroke
hypersensitivity to (evolocumab or) any of the excipients found in the drug product
use of estrogen therapy
current use of antithrombotic or anticoagulant therapy
known bleeding tendency that would be an contraindication to heparin test
history of cancer within the past 5 years (except for adequately treated basal cell skin cancer, squamous cell skin cancer or in situ cervical cancer)
women of childbearing potential not protected by effective birth control method and/or not willing to be tested for pregnancy
patient considered by the investigator or any sub-investigator as inappropriate for this study for any reason