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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
Abstract
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 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 HbA1c 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.
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“Pemafibrate, a selective peroxisome proliferator-activated receptor α modulator, reduces triglyceride levels and improves other lipid levels.”
From Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk (2022) · cites this paper as [13]
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“Phase 2 studies have shown that, as compared with PPARα agonists such as fenofibrate, pemafibrate had greater triglyceride-lowering and HDL cholesterol-raising actions with fewer off-target effects. 9-14”
From Triglyceride Lowering with Pemafibrate to Reduce Cardiovascular Risk (2022) · cites this paper as [13]
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- Matsuba, 2016, The effects of selective PPAR alpha modulator, K-877, on the insulin sensitivity evaluated by glucose clamp test (Abstract), J-Stage, 59, S462
- Araki, 2014, A highly potent and specific PPAR alpha agonist, K-877, improves lipid profiles and insulin sensitivity in dyslipidaemia subjects; an integrated analysis of 3 phase 2/3 trials (Abstract), Diabetologia, 57, S272
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Metadata
- Authors
- Araki, E., Yamashita, S., Arai, H., Yokote, K., Satoh, J., Inoguchi, T., Nakamura, J., Maegawa, H., Yoshioka, N., Tanizawa, Y., Watada, H., Suganami, H., & Ishibashi, S.
- Affiliations
- Kumamoto University (JP)
- Rinku General Medical Center (JP)
- National Center for Geriatrics and Gerontology (JP)
- Chiba University (JP)
- Tohoku Medical and Pharmaceutical University Wakabayashi Hospital (JP)
- Fukuoka Health Promotion Support Center, Fukuoka, Japan
- Aichi Medical University (JP)
- Shiga University of Medical Science (JP)
- NTT Medical Center Sapporo (JP)
- Yamaguchi University (JP)
- Juntendo University (JP)
- Kowa (Japan) (JP)
- Jichi Medical University (JP)
- Corresponding author
- Araki, Eiichi
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2018-01-03
- Volume
- 41
- Issue
- 3
- Pages
- 538-546
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2782064714
- Cited by
- 164
- References
- 38
- Citations by year
- 2026: 10 · 2025: 12 · 2024: 17 · 2023: 17 · 2022: 20 · 2021: 25 · 2020: 17 · 2019: 32 · 2018: 13
- FWCI
- 7.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (17K19643, 17H04201, 17H02100, 18K08482, 15H04849)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- pemafibrate, PPARα agonist, type 2 diabetes, hypertriglyceridemia, dyslipidemia, triglyceride lowering, remnant cholesterol, apolipoprotein B, apolipoprotein C-III, HDL cholesterol, apolipoprotein A-I, insulin resistance, FGF21, glucose metabolism, drug safety
- MeSH terms
- Aged, Benzoxazoles, Blood Glucose, Butyrates, Diabetes Mellitus, Type 2, Double-Blind Method, Female, Humans, Lipids, Male, Middle Aged, Placebos, Hypertriglyceridemia, PPAR alpha, Lipid Metabolism
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