BACKGROUND Close observation, statins, fibrate treatment, and lifestyle changes can safely manage asymptomatic individuals with severe hypertriglyceridemia (HTG) and minimal risk of symptom development. However, the risk of medication-induced liver injury in patients taking statin-fibrate makes management more challenging, and may require hospital admission and close monitoring with follow-up. CASE REPORT We present a rare case of a 43-year-old man with asymptomatic severe HTG exceeding 11.370 mg/dL with mixed hyperlipidemia, managed initially with high-intensity statins and fibrate. However, due to the concurrent use of statin and fibrates, the patient subsequently developed an acute liver injury. Hence, the oral medications had to be stopped, and the patient was admitted to the hospital for an insulin drip. Even during the hospital course, the patient\'s triglyceride (TG) levels showed resistance to the recommended dose of insulin and he required a higher insulin dose. He was discharged on fenofibrate and subcutaneous insulin to keep the TG level under 500. Fibrate was stopped, and high-intensity statin was used as primary prevention with lifestyle modifications. CONCLUSIONS This instance highlights the necessity of increased cognizance and cooperative endeavors in handling severe asymptomatic HTG. Our results highlight the significance of further research into the management of severe asymptomatic HTG in cases of injury to the liver. This work adds essential knowledge to the ongoing discussion about managing a rare case complicated by acute liver injury.

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.

Phototherapy is the standard treatment for neonatal jaundice. We aimed to review the efficacy and safety of fenofibrate as an adjunct therapy. Twelve databases were searched and a systematic review and meta-analysis were conducted. Mean change (MC), mean difference (MD), and risk ratios (RR) with a 95% confidence interval (CI) were calculated using a random effects model. The GRADE approach was used to evaluate the evidence\'s certainty. Nine randomized trials were included. The MC of total serum bilirubin (mg/dL) was significant at 12, 24, 36, 48, and 72 h with respective MC (95% CI) values of -0.46 (-0.61, -0.310), -1.10 (-1.68, -0.52), -2.06 (-2.20, -1.91), -2.15 (-2.74, -1.56), and -1.13 (-1.71, -0.55). The FEN + PT group had a shorter duration of phototherapy (MD: -14.36 h; 95% CI: -23.67, -5.06) and a shorter hospital stay (MD: -1.40 days; 95% CI: -2.14, -0.66). There was no significant difference in the risk of complications (RR: 0.89; 95% CI: 0.54, 1.46) or the need for exchange transfusion (RR: 0.58; 95% CI: 0.12, 2.81). The certainty of the evidence was very low for all outcomes. In conclusion, fenofibrate might be a safe adjunct to neonatal phototherapy. Larger randomized controlled trials are needed for the confirmation of these results.

BACKGROUND: Pemafibrate is a novel fibrate class drug that is a highly potent and selective agonist of peroxisome proliferator-activated receptor α (PPARα). We performed the first ever network meta-analysis containing the largest ever group of patients to test the efficacy of pemafibrate in improving lipid levels compared with fenofibrate and placebo in patients with dyslipidemia.
METHODS: Potentially relevant clinical trials were identified in Medline, PubMed, Embase, clinicaltrials.gov, and Cochrane Controlled Trials registry. Nine randomized controlled trials met the inclusion criteria out of 40 potentially available articles. The primary effect outcome was a change in the levels of triglycerides (TG), high-density lipoproteins (HDL), or low-density lipoproteins (LDL) before and after the treatment.
RESULTS: A total of 12,359 subjects were included. The mean patient age was 54.73 (years), the mean ratio for female patients was 18.75%, and the mean examination period was 14.22 weeks. The dose for pemafibrate included in our study was 0.1, 0.2, or 0.4 mg twice daily, whereas the dose for fenofibrate was 100 mg/day. Data showed a significant reduction in TG and a mild increase in HDL levels across the pemafibrate group at different doses and fenofibrate 100 mg group (with greatest effect observed with pemafibrate 0.1 mg twice daily). A mild increase in LDL was also observed in all groups, but the increase in LDL in the 0.1 mg twice daily dose group was statistically insignificant.
CONCLUSIONS: Pemafibrate 0.1 mg twice daily dose led to highest reduction in TG levels and the highest increase in HDL levels compared with other doses of pemafibrate, fenofibrate, and placebo.

BACKGROUND: Many commonly used drugs were evaluated as repurposed treatment options since the emergence of the COVID-19 pandemic. The benefit of lipid-lowering agents has been controversial in this regard. In this systematic review, we assessed the effect of these medications as adjunctive therapy in COVID-19 by the inclusion of randomized controlled trials (RCTs).
METHODS: We searched four international databases including PubMed, the Web of Science, Scopus, and Embase for RCTs in April 2023. The primary outcome was mortality, while other efficacy indices were considered secondary outcomes. In order to estimate the pooled effect size of the outcomes, considering the odds ratio (OR) or standardized mean difference (SMD) and 95% confidence interval (CI), random-effect meta-analyses was conducted.
RESULTS: Ten studies involving 2,167 COVID-19 patients using statins, omega-3 fatty acids, fenofibrate, PCSK9 inhibitors, and nicotinamide as intervention compared to control or placebo, were included. No significant difference was found in terms of mortality (OR 0.96, 95% CI 0.58 to 1.59, p-value = 0.86, I2 = 20.4%) or length of hospital stay (SMD -0.10, 95% CI -0.78 to 0.59, p-value = 0.78, I2 = 92.4%) by adding a statin to the standard of care. The trend was similar for fenofibrate and nicotinamide. PCSK9 inhibition, however, led to decreased mortality and an overall better prognosis. Omega-3 supplementation showed contradicting results in two trials, suggesting the need for further evaluation.
CONCLUSIONS: Although some observational studies found improved outcomes in patients using lipid-lowering agents, our study found no benefit in adding statins, fenofibrate, or nicotinamide to COVID-19 treatment. On the other hand, PCSK9 inhibitors can be a good candidate for further assessment. Finally, there are major limitations in the use of omega-3 supplements in treating COVID-19 and more trials are warranted to evaluate this efficacy.

The prevalence of diabetic retinopathy (DR), and associated morbidity is high in the Asia-Pacific region. Emerging evidence suggests a potential role for fenofibrate in the prevention of progression of DR, especially in patients with cardiovascular risk, and pre-existing mild-to-moderate DR. Fenofibrate has also been found to reduce maculopathy, and the need for laser treatment in these patients. Considering these benefits of fenofibrate, a group of experts from the fields of endocrinology and ophthalmology convened in May 2017, to discuss on the the mechanism of action, and clinical efficacy of fenofibrate in DR. The findings from key clinical studies on fenofibrate in DR were reviewed by the experts, and consensus statements were derived to define the role of fenofibrate in the prevention and treatment of DR. The statements were rated based on the GRADE criteria. An algorithm was also developed for the screening and treatment of DR in patients with type 2 diabetes (T2D), and the place of fenofibrate was defined in the algorithm. The expert recommendations, and the algorithm provided in this review will serve as a guide to the clinicians to reconsider the adjunctive use of fenofibrate for preventing the progression of DR in selected T2D patients.

HMG-CoA reductase inhibitors (statins), lipoprotein lipase activators (PPARα agonists) or fibrates are commonly used for controlling increased lipid levels in hyperlipidemia. Fenofibrate (FEN) belongs to the second generation prodrug fibric acid (isobutyric acid) derivative belonging to lipoprotein lipase activator class of drug. Results of clinical studies suggest that FEN can substantially reduce severe acute respiratory syndrome coronavirus 2. alpha and beta variant infection in human cell efficiently. This review article provides an in-depth examination of critical analytical methodologies used in the pharmaceutical analysis of FEN in pure forms, biological samples and pharmaceuticals. According to literature study reports several analytical techniques have been used for determination of FEN alone or in the combined dosage forms. Based on the literature, it was determined that high-performance liquid chromatography and UV/vis-spectrophotometry are the most widely used methods for FEN analysis. Sahoo et al. have developed the best HPLC method in bulk and pharmaceutical dosage form with the retention time of 19.268 min using phosphate buffer (pH 3.0): acetonitrile in the ratio of 30:70 (% v/v) as mobile phase. The information presented here may provide a solid foundation for future research on FEN in the field of drug analysis.

Although studies of nonstatin lipid-lowering therapies have demonstrated cardiovascular benefits; whether these benefits provide good value has not been evaluated in type 2 diabetes mellitus patients. A systematic review was performed to include studies on the cost-effectiveness of non-statin lipid-lowering therapies in type 2 diabetes mellitus patients with/without cardiovascular disease. Thirteen studies were included; ezetimibe (n = 8), proprotein convertase subtilisin/kexin type 9 inhibitors (n = 4), fenofibrate (n = 2), nicotinic acid (n = 1), extended-release niacin/laropiprant (n = 1), and icosapent ethyl (n = 1). Six studies considered ezetimibe + statin to be a cost-effective compared to statins monotherapy, three studies suggested that proprotein convertase subtilisin/kexin type 9inhibitors + statins were not cost-effective compared to statin + ezetimibe. Fenofibrate was a cost-effective either as monotherapy or combined with a statin compared to statin or fenofibrate monotherapy. Nicotinic acid and proprotein convertase subtilisin/kexin type 9 compared to statin monotherapy were also cost-effective. Icosapent ethyl was cost-effective compared to standard care but not using the wholesale acquisition cost.

BACKGROUND: This meta-analysis aimed to evaluate the effectiveness of fibrates in the treatment of pruritus in patients with primary biliary cholangitis (PBC), so as to guide the clinical treatment of such cases.
METHODS: Searches of the PubMed, Google Scholar, and Cochrane Library databases were performed to identify randomized controlled trials (RCTs) and prospective studies published up to December 2020 that used bezafibrate and fenofibrate as treatments for pruritus in patients with PBC. Data extraction and quality evaluation of the included literature were performed. Review Manager 5.3 software was employed for statistical analysis of the data.
RESULTS: This meta-analysis included 7 studies, comprising 382 patients with PBC, which assessed the efficacy of bezafibrate and fenofibrate for treating pruritus. The results showed that treatment with fibrates significantly improved pruritus symptoms in patients with PBC [relative risk (RR) =6.52, 95% confidence interval (CI): 3.26-13.06, P<0.00001]. Subgroup analysis revealed that in comparison with fenofibrate (RR =5.34, 95% CI: 0.88-32.62, P=0.07), bezafibrate (RR =25.87, 95% CI: 7.93-84.42, P<0.00001) was more effective in improving pruritic symptoms in patients with PBC. Bezafibrate was also superior to fenofibrate in reducing the degree of pruritus in patients (mean difference =3.36, 95% CI: 2.62-4.09, P=0.05, I2=73%).
CONCLUSIONS: Fibrates can significantly improve pruritus symptoms in patients with PBC but only in a subset of patients. Further studies are needed to elucidate the pathophysiological mechanisms underlying the effect of fibrates on pruritus in PBC, and thus guide future treatment regimens.

Fenofibrate is a marketed fibric acid derivative for lipid-lowering in patients with lipid disorders. Numerous studies have proven fenofibrate had a certain effect on serum uric acid, here we conducted this study to quantitatively assess the effect of fenofibrate intervention in modulating serum uric acid concentration and the influence on serum creatinine. The PubMed, Embase and Cochrane were systematically searched for randomized controlled trials update to January, 2020. Primary endpoints focused on serum uric acid concentration and serum creatinine concentration. The pooled effects were calculated as weighted mean difference (WMD) by a random-effects model. Finally, 9 studies representing 487 patients were included in the meta-analysis. The meta-analysis demonstrated that fenofibrate significantly reduced serum uric acid levels (WMD -1.32 mg/dL, 95%CI -1.61 to -1.03, p < 0.001) and an elevated level in serum creatinine (WMD 0.09 mg/dL, 95%CI 0.02 to 0.15, p < 0.001) following fenofibrate therapy compared with placebo. The present study provided strong evidence that fenofibrate intervention exerted a significant reduction on serum uric acid and a mild increase on serum creatinine. Meta-analysis suggested that there were no significant association between the serum uric acid lowering effect with either dose or treatment duration. Overall, our meta-analysis ascertained that fenofibrate have potential therapeutic effects in patients with lipid metabolic abnormalities but with mid nephrotoxicity. There is strong evidence to provide future direction of practical application and clinical researches of fenofibrate.