Efficacy and Safety of Prolonged Treatment with Pemafibrate plus an HMG-CoA Reductase Inhibitor in Japanese Patients with Type 2 Diabetes Mellitus

Abstract

It has been suggested that caution should be exercised when using HMG-CoA reductase inhibitor (statin) in combination with a drug of the fibrate family because of the potentially elevated risk of development of hepatic function impairment and myopathy. We conducted this present study to evaluate the efficacy and safety of treatment with a statin plus pemafibrate (a new fibrate) versus treatment with pemafibrate alone in Japanese patients with type 2 diabetes mellitus.

In this study, a total of 23 Japanese patients with type 2 diabetes mellitus were divided into two groups: a group that received pemafibrate alone and a group that received pemafibrate+a statin for a period of 3 years, respectively. Blood levels of lipids and hepatic and renal function parameters were measured before and one and three years after the start of treatment.

The pemafibrate-alone group showed reduction of the blood lipid levels, but no adverse changes of the hepatic or renal function parameters were observed. Similarly, the combined pemafibrate+statin treatment group also showed lowering of the blood lipid levels without any adverse changes of the parameters.

Improvement of the blood lipid profile was observed in patients who received prolonged treatment with pemafibrate. Similarly, improvement of the blood lipid profile without any adverse changes of the hepatic or renal function parameters was also observed in patients who received prolonged combined pemafibrate+statin treatment. Thus, our findings confirm the safety and efficacy of pemafibrate administered either alone or in combination with a statin.

Keywords

pemafibrate - statin - combined treatment - type 2 diabetes mellitus

Publication History

Received: 24 September 2024

Accepted: 15 March 2025

Article published online:
21 May 2025

• References

• 1 American Diabetes Association. Role of cardiovascular risk factors in prevention and treatment of macrovascular disease in diabetes. Diabetes Care 1989; 12: 573-579
• 2 Goldstein JL, Hazzard WR, Schrott HG. et al. Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest 1973; 52: 1533-1543
• 3 Catapano AL, Graham I, De Backer G. et al. 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
• 4 Chapman MJ, Redfern JS, McGovern ME. et al. Niacin and fibrates in atherogenic dyslipidemia: pharmacotherapy to reduce cardiovascular risk. Pharmacol Ther 2010; 126: 314-345
• 5 Koh KK, Han SH, Quon MJ. et al. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care 2005; 28: 1419-1424
• 6 Koh KK, Quon MJ, Lim S. et al. Effects of fenofibrate therapy on circulating adipocytokines in patients with primary hypertriglyceridemia. Atherosclerosis 2011; 214: 144-147
• 7 Koh KK, Quon MJ, Shin KC. et al. Significant differential effects of omega-3 fatty acids and fenofibrate in patients with hypertriglyceridemia. Atherosclerosis 2012; 220: 537-544
• 8 Kusunoki M, Sakazaki T, Tsutsumi K. et al. The effects of pemafibrate in Japanese patients with type 2 diabetes receiving HMG-CoA reductase inhibitors. Endocrine, Metabolic & Immune Disorder-Drug Target (EMIDDT) 2021; 21: 919-924
• 9 Ishibashi S, Yamashita S, Arai H. et al. 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
• 10 Arai H, Yamashita S, Yokote K. et al. 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
• 11 Boekholdt SM, Arsenault BJ, Mora S. et al. 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: 1302-1309
• 12 Shimano H, Arai H, Harada-Shiba M. et al. Proposed guidelines for hypertriglyceridemia in Japan with non-HDL cholesterol as the second target. J Atheroscler Thromb 2008; 15: 116-121