A Significant Increase of Estimated Glomerular Filtration Rate After Switching From Fenofibrate to Pemafibrate in Type 2 Diabetic Patients

Abstract

Background Dyslipidemia is one of the major risk factors for cardiovascular disease (CVD), along with hypertension, diabetes, smoking and obesity. Approximately 70% of CVD risk remains even after treatment of elevated low-density lipoprotein-cholesterol (LDL-C) by statins. High triglyceride (TG) and low high-density lipoprotein-cholesterol (HDL-C) level are potential therapeutic targets to prevent CVD. Fibrates were associated with a greater reduction in TG, and a greater increase in HDL-C. Fibrates activate specific transcription factors belonging to the nuclear hormone receptor superfamily, termed peroxisome proliferator-activated receptors (PPARs). Fibrates improve atherogenic dyslipidemia by mediating PPARα. Pemafibrate is a novel member of the selective PPARα modulator (SPPARMα) family that was designed to have a higher PPARα agonistic activity and selectivity than previous fibrates. Here, we aimed to study the influences of the switching from fenofibrate to pemafibrate on metabolic parameters in type 2 diabetic patients. Methods We retrospectively picked up type 2 diabetic patients who had undergone the switching from fenofibrate to pemafibrate, and compared metabolic parameters before the switching with the data at 3, 6 and 12 months after the switching. Results We found 15 patients with type 2 diabetes. Serum alanine aminotransferase significantly decreased at 6 months after the switching as compared with baseline. The estimated glomerular filtration rate (eGFR) significantly increased at 3, 6 and 12 months after the switching from fenofibrate to pemafibrate as compared with baseline. Serum uric acid (UA) levels significantly increased at 3 and 6 months after the switching as compared with baseline. We did not observe changes in other metabolic parameters after the switching. Conclusion We observed a significant increase of eGFR and serum UA after the switching from fenofibrate to pemafibrate in type 2 diabetic patients. Recent evidences suggest that the improvement of eGFR is beneficially associated with the development of CVD in type 2 diabetic patients. Considering the impact on eGFR, pemafibrate may effectively reduce CVD as compared with fenofibrate.

Effects of a Novel Selective Peroxisome Proliferator-Activated Receptor α Modulator, Pemafibrate, on Metabolic Parameters: A Retrospective Longitudinal Study

“…However, reduction of serum UA by pemafibrate was not reported. Fenofibrate has URAT1 inhibitory effect, but pemafibrate may not have such effect, which was supported by our recent study that showed a significant increase of serum UA after the switching from fenofibrate to pemafibrate [ 60 ]. In this study, pemafibrate may decrease serum UA by reducing over-expressed URAT1 and GLUT9 due to insulin resistance, and by improving systemic insulin resistance, which may be supported by a significant and positive correlation between changes in serum UA and changes in TG at 12 months after the start of pemafibrate.…”

A Significance of Selective Inhibition of Urate Transporter 1 and Non-Inhibition of Adenosine Triphosphate-Binding Cassette Transporter in Renal Function in a Patient With Advanced Stage Chronic Kidney Disease

“…Topiroxostat was reported to inhibit ABCG2 [8], which may lead to increase in serum creatinine due to reduced excretion of IS. We previously reported a significant increase in estimated glomerular filtration rate (eGFR), in spite of an increase in serum UA, by the switching from fenofibrate which inhibits ABCG2 to pemafibrate in type 2 diabetic patients [8,9], supporting an importance of ABCG2 for renal function. Hyperuricemia was associated with a greater incidence of end-stage renal disease [10].…”

A Possible Exquisite Crosstalk of Urate Transporter 1 With Other Urate Transporters for Chronic Kidney Disease and Cardiovascular Disease Induced by Dotinurad

“…We previously reported that the switching from fenofibrate to the selective peroxisome proliferator-activated receptor (PPAR) α modulator, pemafibrate, increased serum uric acid (UA) levels and reduced estimated glomerular filtration rate (eGFR) in patients with dyslipidemia [ 1 ]. Fenofibrate has a property to decrease serum UA by inhibition of urate transporter 1 (URAT1) by its major metabolite [ 2 ].…”

“…Although fenofibrate was reported to decrease the eGFR [ 3 ], the mechanism of fenofibrate-induced renal impairment has been remained unclear. Further, our previous discussion on such issue was premature [ 1 ]. Recently, the role of UA transporters has been clarified [ 4 ] ( Fig.…”