IDF21-0056 Effects of pemafibrate on lipid metabolism in patients with hypertriglyceridemia complicated with type 2 diabetes

Background: Pemafibrate is a novel selective peroxisome proliferator-activated receptor modulator that significantly ameliorated lipid abnormalities in a relatively small number of patients with type 2 diabetes (T2D) in a phase 3 trial. It represents a current treatment for dyslipidemia, presumably being beneficial effects on liver diseases, such as non-alcoholic liver disease/non-alcoholic steatohepatitis, and diabetic microvascular complications. However, the effects of pemafibrate have not been characterized in real-world clinical practice in patients with T2D. Aim: We aimed to determine the effects of pemafibrate on the lipid profile as well as other metabolic parameters of patients with T2D and hypertriglyceridemia. Method: We have been performing a multi-center, prospective, observational study at nine institutions since July 2019. Patients of >20 years with T2D and hypertriglyceridemia were enrolled after obtaining their written informed consent. Hypertriglyceridemia is defined as a fasting triglyceride (TG) concentration of ≥150 mg/dL (1.7 mmol/L) or the use of fibrates. The major exclusion criteria are: hypersensitivity to pemafibrate, pregnancy, and serious liver or kidney dysfunction. There are two arms: in the Pemafibrate group, participants are started on 0.2–0.4 mg/day pemafibrate or switched from another fibrate to pemafibrate; whereas in the Control group, participants continue their existing fibrate or do not undergo antihyperlipidemic treatment. Clinical and laboratory data, including metabolic parameters and indices of liver and renal function, are collected after an overnight fast at baseline, and after 12, 24, and 52 weeks. Body mass, abdominal circumference, and systolic and diastolic blood pressure are also measured at each study visit. The primary outcomes are the changes in fasting serum TG and high-density lipoprotein-cholesterol concentrations (HDL-C) between baseline and at 52-wks, and these will be compared between the Pemafibrate and Control groups. The secondary outcomes are the changes in other lipid parameters, such as apolipoproteins (A1, B, and E) and small, dense low-density lipoprotein-cholesterol (LDL-C), which is assessed using the LDL-migration index or LDL-C/Apo-B. Additionally, the changes in glucose metabolism, insulin sensitivity, renal function, and markers of liver steatosis and fibrosis markers are secondary outcomes. To balance the characteristics of the groups, propensity score matching (1:1) will be performed at the end of the study. The study is registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000037385). The study protocol was approved by the Hokkaido University Certified Review Board (018-0440) and the study was carried out in accordance with the principles of the Declaration of Helsinki and its amendments. Results: All the participants have now been enrolled and the study is in the observation phase. At baseline, 664 Japanese participants were included. Of them, 318 are in the Pemafibrate group and 346 in the Control group. The median age of the participants was 62 years and 35.3% were women. The median TG and HDL-C concentrations were 177 mg/dL and 49 mg/dL, respectively. The mean systolic/diastolic blood pressure was 130/75 mmHg, the mean body mass index 27.0 kg/m2, and the mean HbA1c 7.0% (57 mmol/mol). The results of this study will be disclosed in December 2021.