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Endocrine, Metabolic & Immune Disorders - Drug Targets


ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

Research Article

The Effects of Pemafibrate in Japanese Patients with Type 2 Diabetes Receiving HMG-CoA Reductase Inhibitors

Author(s): Masataka Kusunoki*, Takahiko Sakazaki, Kazuhiko Tsutsumi, Tetsuro Miyata and Yoshiharu Oshida

Volume 21 , Issue 5 , 2021

Published on: 18 August, 2020

Page: [919 - 924] Pages: 6

DOI: 10.2174/1871530320999200818135553

Price: $65


Objective: The combination therapy of HMG-CoA reductase inhibitors (statins), which are anti-hyperlipidemic agents, and fibrates may increase the risk of hepatic dysfunction and myopathy, therefore, this combination required careful administration for patients. In the present study, the effects of combination therapy of pemafibrate, a novel fibrate, and statins, was evaluated.

Methods: Pemafibrate was administered for 6 months as an add-on to statin therapy in 27 type 2 diabetes patients with dyslipidemia already receiving statins for 6 months (combination group), and the efficacy and safety of the combination therapy in comparison with a pemafibrate monotherapy group was examined.

Results: In the combination group, a decrease in serum total cholesterol levels was observed after 6 months of pemafibrate treatment compared to baseline, along with an increase in HDL-cholesterol. While serum triglyceride level was reduced, HbA1c level was elevated in both the groups. Serum creatinine kinase level, which is an indicator of myopathy, was lowered in the combination group. In addition, a decrease in γ-glutamyl transpeptidase, a parameter of hepatic dysfunction, was observed in the combination group.

Conclusion: The statin-pemafibrate combination therapy in type 2 diabetes patients with dyslipidemia improved lipid metabolism safely without increasing the risk of hepatic dysfunction and myopathy.

Keywords: Pemafibrate, statin, myopathy, hepatic dysfunction, type 2 diabetes, Japanese patients.

Graphical Abstract
American Diabetes Association. Role of cardiovascular risk factors in prevention and treatment of macrovascular disease in diabetes. Diabetes Care, 1989, 12(8), 573-579.
[] [PMID: 2673697]
Goldstein, J.L.; Hazzard, W.R.; Schrott, H.G.; Bierman, E.L.; Motulsky, A.G. Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. J. Clin. Invest., 1973, 52(7), 1533-1543.
[] [PMID: 4718952]
Catapano, A.L.; Graham, I.; De Backer, G.; Wiklund, O.; Chapman, M.J.; Drexel, H.; Hoes, A.W.; Jennings, C.S.; Landmesser, U.; Pedersen, T.R.; Reiner, Ž.; Riccardi, G.; Taskinen, M.R.; Tokgozoglu, L.; Verschuren, W.M.; Vlachopoulos, C.; Wood, D.A.; Zamorano, J.L. Authors/Task Force Members. 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: The Task Force for the Management of Dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis, 2016, 253, 281-344.
[] [PMID: 27594540]
Lamprea-Montealegre, J.A.; Sharrett, A.R.; Matsushita, K.; Selvin, E.; Szklo, M.; Astor, B.C. Chronic kidney disease, lipids and apolipoproteins, and coronary heart disease: the ARIC study. Atherosclerosis, 2014, 234(1), 42-46.
[] [PMID: 24607852]
Chapman, M.J.; Redfern, J.S.; McGovern, M.E.; Giral, P. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol. Ther., 2010, 126(3), 314-345.
[] [PMID: 20153365]
Koh, K.K.; Han, S.H.; Quon, M.J.; Yeal Ahn, J.; Shin, E.K. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care, 2005, 28(6), 1419-1424.
[] [PMID: 15920062]
Koh, K.K.; Quon, M.J.; Lim, S.; Lee, Y.; Sakuma, I.; Lee, Y.H.; Han, S.H.; Shin, E.K. Effects of fenofibrate therapy on circulating adipocytokines in patients with primary hypertriglyceridemia. Atherosclerosis, 2011, 214(1), 144-147.
[] [PMID: 21075373]
Koh, K.K.; Quon, M.J.; Shin, K.C.; Lim, S.; Lee, Y.; Sakuma, I.; Lee, K.; Han, S.H.; Shin, E.K. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Atherosclerosis, 2012, 220(2), 537-544.
[] [PMID: 22153696]
Ishibashi, S.; Yamashita, S.; Arai, H.; Araki, E.; Yokote, K.; Suganami, H.; Fruchart, J.C.; Kodama, T. K-877-04 Study Group. Effects of K-877, a novel selective PPARα modulator (SPPARMα), in dyslipidaemic patients: A randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis, 2016, 249, 36-43.
[] [PMID: 27062408]
Arai, H.; Yamashita, S.; Yokote, K.; Araki, E.; Suganami, H.; Ishibashi, S. K-877 Study Group. 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. Atherosclerosis, 2017, 261, 144-152.
[] [PMID: 28410749]
Boekholdt, S.M.; Arsenault, B.J.; Mora, S.; Pedersen, T.R.; LaRosa, J.C.; Nestel, P.J.; Simes, R.J.; Durrington, P.; Hitman, G.A.; Welch, K.M.; DeMicco, D.A.; Zwinderman, A.H.; Clearfield, M.B.; Downs, J.R.; Tonkin, A.M.; Colhoun, H.M.; Gotto, A.M., Jr; Ridker, P.M.; Kastelein, J.J. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA, 2012, 307(12), 1302-1309.
[] [PMID: 22453571]
Shimano, H.; Arai, H.; Harada-Shiba, M.; Ueshima, H.; Ohta, T.; Yamashita, S.; Gotoda, T.; Kiyohara, Y.; Hayashi, T.; Kobayashi, J.; Shimamoto, K.; Bujo, H.; Ishibashi, S.; Shirai, K.; Oikawa, S.; Saito, Y.; Yamada, N. Proposed guidelines for hypertriglyceridemia in Japan with non-HDL cholesterol as the second target. J. Atheroscler. Thromb., 2008, 15(3), 116-121.
[] [PMID: 18603817]
Ishibashi, S.; Arai, H.; Yokote, K.; Araki, E.; Suganami, H.; Yamashita, S. K-877 Study Group. Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor α modulator, in patients with dyslipidemia: Results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J. Clin. Lipidol., 2018, 12(1), 173-184.
[] [PMID: 29203092]
Yamashita, S.; Arai, H.; Yokote, K.; Araki, E.; Matsushita, M.; Nojima, T.; Suganami, H.; Ishibashi, S. Efficacy and safety of pemafibrate, a novel selective peroxisome proliferator-activated receptor α modulator (SPPARMα): pooled analysis of phase 2 and 3 studies in dyslipidemic patients with or without statin combination. Int. J. Mol. Sci., 2019, 20, 5537.

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