Dose-dependent efficacy and renal safety of pemafibrate versus fenofibrate in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and hypertriglyceridemia: a multicenter randomized controlled, open label trial
Year: 2026
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Background No randomized controlled trial has directly compared the efficacy of pemafibrate to that of fenofibrate, or evaluated the dose–response relationship of pemafibrate in metabolic dysfunction–associated steatotic liver disease (MASLD). Therefore, we compared the efficacy and safety of high- and low-dose pemafibrate versus fenofibrate over 48 weeks in patients with MASLD and hypertriglyceridemia. Methods This multicenter, open-label, prospective, randomized controlled phase 4 trial (the PRESENT study) included 360 patients with MASLD and hypertriglyceridemia at 29 sites in Japan between December 23, 2020, and March 31, 2026. Participants were randomly assigned (1:1:1) to high-dose pemafibrate (0.4 mg/day; PEM-H), low-dose pemafibrate (0.2 mg/day; PEM-L), or fenofibrate (53.3–106.6 mg/day; FENO) groups. The primary endpoint was change in alanine aminotransferase (ALT) levels at Week 24. Secondary endpoints included liver fibrosis markers, renal parameters, magnetic resonance elastography (MRE), and adverse events. The trial was registered in the Japan Registry of Clinical Trials on December 28, 2020 (jRCTs031200280). Findings At Week 24, PEM-H and PEM-L produced significantly greater ALT reductions than FENO (p < 0.001 and p=0.015, respectively). Exploratory comparison revealed greater reduction for PEM-H than PEM-L (p = 0.018, Holm adjustment), suggesting a dose-dependent effect. Higher baseline ALT levels and lean phenotypes were independently associated with ALT response. At Week 48, Mac-2 binding protein glycosylation isomer decreased significantly in PEM-H and PEM-L compared with a modest reduction in FENO (p < 0.001 and p < 0.001, respectively). MRE demonstrated significant decreases in liver stiffness in PEM-H and PEM-L compared with FENO (p < 0.05 and p=0.02, respectively). Percentage change in serum creatinine levels was lower in PEM-H and PEM-L than in FENO. No treatment-related serious adverse events were observed in any of the three groups. Interpretation Pemafibrate demonstrated greater reductions in ALT levels than fenofibrate, with a notable dose–response relationship and favorable safety profile, suggesting therapeutic potential for patients with MASLD and hypertriglyceridemia. Funding This study was funded by the Kowa Company, Ltd. (Tokyo, Japan).
Source: EClinicalMedicine
Authors: Michihiro Iwaki, Hiroshi Tobita, Yuya Seko, Kazuhito Kawata, Kento Imajo, Koki Nagai, Takaomi Kessoku, Eiji Sakai, Yoshinobu Nakada, Satoshi Koyama, Takeo Kurihashi, Wataru Yoshioka, Shuzo Yunotani, Toshikazu Kohira, Kano Takahashi, Midori Yamamoto, Yuko Ishimaru, Noriko Oza, Yuki Yamaguchi, Shinji Iwane, Takeshi Chida, Fujito Kageyama, Yuzo Sasada, Masahiro Matsushita, Akimitsu Tadauchi, Gou Murohisa, Shuichi Sato, Kazuhisa Maeda, Koichiro Furuta, Ryuta Shigefuku, Masahiro Koseki, Takaaki Sugihara, Nobuharu Tamaki, Motoh Iwasa, Takumi Kawaguchi, Tomohisa Takagi, Miwa Kawanaka, Atsushi Kawaguchi, Atsushi Nakajima, Masato Yoneda, Hirokazu Takahashi
Institutions: Yokohama City University, Shimane University Hospital, Kyoto Prefectural University of Medicine, Hamamatsu University School of Medicine, Shin-yurigaoka General Hospital, National Hospital Organization Yokohama Medical Center, Narita Hospital, International University of Health and Welfare Narita Hospital, International University of Health and Welfare, Yokohama Sakae Kyosai Hospital, St. Marianna University School of Medicine, Kanagawa Dental University Yokohama Clinic, Saga-Ken Medical Centre Koseikan, Saga University, Japanese Red Cross Karatsu Hospital, Masuda Red Cross Hospital, Hamamatsu Medical Center, Iwata City Hospital, Seirei Mikatabara General Hospital, Seirei Hamamatsu General Hospital, National Hospital Organization Hamada Medical Center, Mie University, Mie University Hospital, The University of Osaka, Tottori University, Musashino Red Cross Hospital, Kurume University, Okayama University, Kawasaki Medical School, International University Of Health And Welfare Atami Hospital
Language: English
Subfield: Hepatology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,780
Funder: Kowa Company
OpenAlex ID: W7220725480