Effects of Pemafibrate, a Novel Selective PPARa Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial Diabetes Care 2018;41:538–546 | https://doi.org/10.2337/dc17-1589 OBJECTIVE Type 2 diabetes is frequently complicated with atherogenic dyslipidemia. This study aimed to evaluate the efficacy and safety of pemafibrate (K-877) in patients with type 2 diabetes comorbid with hypertriglyceridemia. RESEARCH DESIGN AND METHODS Patients were randomly assigned to three groups and received placebo (n = 57), 0.2 mg/day pemafibrate (n = 54), or 0.4 mg/day pemafibrate (n = 55) for 24 weeks (treatment period 1). Subsequently, the patients received follow-up treatment for another 28 weeks (treatment period 2), in which the placebo was switched to 0.2 mg/day pemafibrate. This article presents the results of treatment period 1, which were the primary objectives. RESULTS The pemafibrate groups showed significantly reduced fasting serum triglyceride levels by ∼45% compared with the placebo group (P < 0.001). Additionally, the pemafibrate groups displayed significant decreases in non-HDL and remnant lipo- protein cholesterol, apolipoprotein (Apo) B100, ApoB48, and ApoCIII levels and sig- nificant increases in HDL cholesterol and ApoA-I levels. LDL cholesterol levels were not considerably altered in the pemafibrate groups. Furthermore, the 0.2 mg/day pemafibrate group showed a significantly reduced HOMA–insulin resistance score compared with the placebo group; however, no significant changes compared with placebo were found in fasting plasma glucose, fasting insulin, glycoalbumin, or HbA 1c levels. The pemafibrate groups also showed significantly increased fibroblast growth factor 21 levels compared with the placebo group. All groups displayed comparable rates of adverse events and drug reactions. CONCLUSIONS Pemafibrate significantly ameliorated lipid abnormalities and was well tolerated in patients with type 2 diabetes comorbid with hypertriglyceridemia. 1 Department of Metabolic Medicine, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan 2 Department of Community Medicine and De- partment of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan 3 Rinku General Medical Center, Osaka, Japan 4 National Center for Geriatrics and Gerontology, Aichi, Japan 5 Department of Clinical Cell Biology and Medi- cine, Chiba University Graduate School of Medi- cine, Chiba, Japan 6 Tohoku Medical and Pharmaceutical University Wakabayashi Hospital, Miyagi, Japan 7 Fukuoka Health Promotion Support Center, Fukuoka, Japan 8 Division of Diabetes, Department of Internal Medicine, Aichi Medical University, Aichi, Japan 9 Department of Medicine, Shiga University of Medical Science, Shiga, Japan 10 Division of Diabetes and Endocrinology, De- partment of Medicine, Sapporo Medical Center, NTT East Corporation, Hokkaido, Japan 11 Division of Endocrinology, Metabolism, Hema- tological Science and Therapeutics, Yamaguchi University Graduate School of Medicine, Yama- guchi, Japan 12 Department of Metabolism and Endocrinol- ogy, Juntendo University Graduate School of Medicine, Tokyo, Japan 13 Clinical Data Science Department, Kowa Com- pany, Ltd., Tokyo, Japan 14 Division of Endocrinology and Metabolism, Department of Medicine, Jichi Medical Univer- sity, Tochigi, Japan Corresponding author: Eiichi Araki, earaki@gpo .kumamoto-u.ac.jp. Received 1 August 2017 and accepted 27 No- vember 2017. Clinical trial reg. no. JapicCTI-142412, clinicaltrials .jp. This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/ suppl/doi:10.2337/dc17-1589/-/DC1. © 2018 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More infor- mation is available at http://www.diabetesjournals .org/content/license. Eiichi Araki, 1 Shizuya Yamashita, 2,3 Hidenori Arai, 4 Koutaro Yokote, 5 Jo Satoh, 6 Toyoshi Inoguchi, 7 Jiro Nakamura, 8 Hiroshi Maegawa, 9 Narihito Yoshioka, 10 Yukio Tanizawa, 11 Hirotaka Watada, 12 Hideki Suganami, 13 and Shun Ishibashi 14 538 Diabetes Care Volume 41, March 2018 EMERGING TECHNOLOGIES AND THERAPEUTICS Downloaded from http://diabetesjournals.org/care/article-pdf/41/3/538/552690/dc171589.pdf by guest on 17 February 2023