Effects of Pemafibrate, a Novel Selective PPARα Modulator, on Lipid and Glucose Metabolism in Patients With Type 2 Diabetes and Hypertriglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial

被引：148

作者：

Araki, Eiichi ^{[1
]}

Yamashita, Shizuya ^{[2
,3
,4
]}

Arai, Hidenori ^{[5
]}

Yokote, Koutaro ^{[6
]}

Satoh, Jo ^{[7
]}

Inoguchi, Toyoshi ^{[8
]}

Nakamura, Jiro ^{[9
]}

Maegawa, Hiroshi ^{[10
]}

Yoshioka, Narihito ^{[11
]}

Tanizawa, Yukio ^{[12
]}

Watada, Hirotaka ^{[13
]}

Suganami, Hideki ^{[14
]}

Ishibashi, Shun ^{[15
]}

机构：

[1] Kumamoto Univ, Fac Life Sci, Dept Metab Med, Kumamoto, Japan

[2] Osaka Univ, Grad Sch Med, Dept Community Med, Osaka, Japan

[3] Osaka Univ, Grad Sch Med, Dept Cardiovasc Med, Osaka, Japan

[4] Rinku Gen Med Ctr, Osaka, Japan

[5] Natl Ctr Geriatr & Gerontol, Aichi, Japan

[6] Chiba Univ, Grad Sch Med, Dept Clin Cell Biol & Med, Chiba, Japan

[7] Tohoku Med & Pharmaceut Univ, Wakabayashi Hosp, Sendai, Miyagi, Japan

[8] Fukuoka Hlth Promot Support Ctr, Fukuoka, Japan

[9] Aichi Med Univ, Dept Internal Med, Div Diabet, Aichi, Japan

[10] Shiga Univ Med Sci, Dept Med, Shiga, Japan

[11] NTT East Corp, Sapporo Med Ctr, Div Diabet & Endocrinol, Dept Med, Sapporo, Hokkaido, Japan

[12] Yamaguchi Univ, Grad Sch Med, Div Endocrinol Metab Hematol Sci & Therapeut, Yamaguchi, Japan

[13] Juntendo Univ, Grad Sch Med, Dept Metab & Endocrinol, Tokyo, Japan

[14] Kowa Co Ltd, Clin Data Sci Dept, Tokyo, Japan

[15] Jichi Med Univ, Dept Med, Div Endocrinol & Metab, Jichi, Tochigi, Japan

来源：

DIABETES CARE | 2018年 / 41卷 / 03期

关键词：

CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; INSULIN SENSITIVITY; SPPARM-ALPHA; IMPROVES DYSLIPIDEMIA; CHOLESTEROL; AGONIST; K-877; RISK; FENOFIBRATE;

D O I：

10.2337/dc17-1589

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

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 similar to 45% compared with the placebo group (P < 0.001). Additionally, the pemafibrate groups displayed significant decreases in non-HDL and remnant lipoprotein cholesterol, apolipoprotein (Apo) B100, ApoB48, and ApoCIII levels and significant 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.

引用

页码：538 / 546

页数：9

共 40 条

[1]

Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα), in combination with statin treatment: Two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia [J].