Diabetes & Metabolism Journal

Original Article

Complications
Switching from Conventional Fibrates to Pemafibrate Has Beneficial Effects on the Renal Function of Diabetic Subjects with Chronic Kidney Disease: Rimi Izumihara, Hiroshi Nomoto, Kenichi Kito, Yuki Yamauchi, Kazuno Omori, Yui Shibayama, Shingo Yanagiya, Aika Miya, Hiraku Kameda, Kyu Yong Cho, So Nagai, Ichiro Sakuma, Akinobu Nakamura, Tatsuya Atsumi, on Behalf of the PARM-TD Study Group; Received October 15, 2023 Accepted November 22, 2023 Published online February 29, 2024; DOI: https://doi.org/10.4093/dmj.2023.0370 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
Fibrates have renal toxicity limiting their use in subjects with chronic kidney disease (CKD). However, pemafibrate has fewer toxic effects on renal function. In the present analysis, we evaluated the effects of pemafibrate on the renal function of diabetic subjects with or without CKD in a real-world clinical setting.
Methods
We performed a sub-analysis of data collected during a multi-center, prospective, observational study of the effects of pemafibrate on lipid metabolism in subjects with type 2 diabetes mellitus complicated by hypertriglyceridemia (the PARM-T2D study). The participants were allocated to add pemafibrate to their existing regimen (ADD-ON), switch from their existing fibrate to pemafibrate (SWITCH), or continue conventional therapy (CTRL). The changes in estimated glomerular filtration rate (eGFR) over 52 weeks were compared among these groups as well as among subgroups created according to CKD status.
Results
Data for 520 participants (ADD-ON, n=166; SWITCH, n=96; CTRL, n=258) were analyzed. Of them, 56.7% had CKD. The eGFR increased only in the SWITCH group, and this trend was also present in the CKD subgroup (P<0.001). On the other hand, eGFR was not affected by switching in participants with severe renal dysfunction (G3b or G4) and/or macroalbuminuria. Multivariate analysis showed that being older and a switch from fenofibrate were associated with elevation in eGFR (both P<0.05).
Conclusion
A switch to pemafibrate may be associated with an elevation in eGFR, but to a lesser extent in patients with poor renal function.

Reviews

Metabolic Risk/Epidemiology
Role of Fenofibrate Use in Dyslipidemia and Related Comorbidities in the Asian Population: A Narrative Review: Chaicharn Deerochanawong, Sin Gon Kim, Yu-Cheng Chang; Diabetes Metab J. 2024;48(2):184-195. Published online January 26, 2024; DOI: https://doi.org/10.4093/dmj.2023.0168

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Abstract PDF Supplementary Material PubReader ePub: Hypertriglyceridemia and decreased high-density lipoprotein cholesterol (HDL-C) persist despite statin therapy, contributing to residual atherosclerotic cardiovascular disease (ASCVD) risk. Asian subjects are metabolically more susceptible to hypertriglyceridemia than other ethnicities. Fenofibrate regulates hypertriglyceridemia, raises HDL-C levels, and is a recommended treatment for dyslipidemia. However, data on fenofibrate use across different Asian regions are limited. This narrative review summarizes the efficacy and safety data of fenofibrate in Asian subjects with dyslipidemia and related comorbidities (diabetes, metabolic syndrome, diabetic retinopathy, and diabetic nephropathy). Long-term fenofibrate use resulted in fewer cardiovascular (CV) events and reduced the composite of heart failure hospitalizations or CV mortality in type 2 diabetes mellitus. Fenofibrate plays a significant role in improving irisin resistance and microalbuminuria, inhibiting inflammatory responses, and reducing retinopathy incidence. Fenofibrate plus statin combination significantly reduced composite CV events risk in patients with metabolic syndrome and demonstrated decreased triglyceride and increased HDL-C levels with an acceptable safety profile in those with high CV or ASCVD risk. Nevertheless, care is necessary with fenofibrate use due to possible hepatic and renal toxicities in vulnerable individuals. Long-term trials and real-world studies are needed to confirm the clinical benefits of fenofibrate in the heterogeneous Asian population with dyslipidemia.

Refocusing Peroxisome Proliferator Activated Receptor-α: A New Insight for Therapeutic Roles in Diabetes: Hannah Seok, Bong Soo Cha; Diabetes Metab J. 2013;37(5):326-332. Published online October 17, 2013; DOI: https://doi.org/10.4093/dmj.2013.37.5.326

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Abstract PDF PubReader

Although glucose-lowering treatment shows some risk lowering effects in cardiovascular diseases, risks of macrovascular and microvascular complications have still remained, and development of new therapeutic strategies is needed. Recent data have shown that peroxisome proliferator activated receptor-α (PPAR-α) plays a pivotal role in the regulation of lipid homeostasis, fatty acid oxidation, cellular differentiation, and immune response such as inflammation or vascularization related to diabetic complication. This review will re-examine the metabolic role of PPAR-α, summarize data from clinical studies on the effect of PPAR-α agonist in diabetes, and will discuss the possible therapeutic role of PPAR-α activation.

Citations

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