Parmodia (pemafibrate) / Kowa - LARVOL DELTA

Effect of pemafibrate on LDL-cholesterol properties in type 2 diabetes and hypertriglyceridemia by lipid management status: PARM-T2D post hoc analysis. (PubMed, J Diabetes Investig) - "Conversely, in those with high baseline LDL-C, both LDL-C and ApoB decreased, reflecting favorable modifications according to baseline LDL-C control status. These findings suggest that pemafibrate exerts beneficial, status-dependent effects on LDL-C properties, potentially reducing cardiovascular risk by improving LDL particle quality and quantity in high-risk patients with diabetes."

Journal • Retrospective data • Cardiovascular • Diabetes • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus • APOB

Efficacy of Pemafibrate in MASLD With Hypertriglyceridemia: An Updated Meta-Analysis of Biochemical, Lipid, and Noninvasive Fibrosis Outcomes (ACG 2026) - "Pemafibrate significantly improved liver enzymes: ALT (12 studies; mean change -20.35 U/L; 95% CI -24.68 to -16.02; I²=69.1%), AST (11 studies; -7.52 U/L; 95% CI -10.34 to -4.70; I²=62.2%), and GGT (12 studies; -34.71 U/L; 95% CI -38.92 to -30.51; I²=0%). Triglycerides decreased significantly (13 studies; -101.89 mg/dL; 95% CI -118.12 to -85.65; I²=80.2%), while HDL-C increased (12 studies; +3.74 mg/dL; 95% CI +2.48 to +4.99; I²=29.5%). FIB-4 did not significantly change (8 studies; -0.071; 95% CI -0.153 to +0.011)."

Non-invasive • Retrospective data • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Neuroprotective effect of a selective peroxisome proliferator-activated receptor alpha modulator in murine cerebral ischemia. (PubMed, Neurosci Res) - "At 6h post-MCAO, pemafibrate reduced cortical IL-1β (P=0.008) and reduced IL-6 in both striatum (P=0.020) and cortex (P=0.013), with attenuation of microtubule-associated protein 2 degradation. These findings suggest that selective PPARα activation ameliorates ischemic brain injury, likely through anti-inflammatory rather than systemic metabolic effects."

Journal • Preclinical • Cardiovascular • CNS Disorders • Dyslipidemia • Inflammation • Ischemic stroke • Vascular Neurology • IL1B • IL6 • PPARA

Selective PPARα Modulator Pemafibrate Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Regulation of Leptin Signaling and Remodeling of Gut Microbiota. (PubMed, Int J Mol Sci) - "Collectively, these findings demonstrate that Pema attenuates MASLD progression by suppressing leptin-mediated metabolic and inflammatory signaling while improving the gut microenvironment. These results highlight SPPARMα as a promising therapeutic strategy for MASLD and support further clinical investigation of Pema as a disease-modifying treatment targeting the gut-liver axis."

Journal • Dyslipidemia • Fibrosis • Hepatology • Hypertriglyceridemia • Immunology • Liver Cirrhosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • COL1A1 • LEP • PPARA • TLR4 • TNFA

ABCA1 as a Gatekeeper of Pancreatic β-Cell Cholesterol Homeostasis: Links Between Lipoprotein Stress, Lipotoxicity, and Insulin Secretion. (PubMed, Nutrients) - "Exendin-4 activates CaMKK/CaMKIV/PREB-dependent transcription, insulin-like growth factor-1 acts through PI3K/Akt/FoxO1 signaling, and pemafibrate increases ABCA1 through PPAR-α-dependent regulation in experimental models. β-cell function depends on the balance among LDLR-dependent cholesterol uptake, PCSK9-mediated receptor regulation, intracellular sterol trafficking and esterification, ABCG1-dependent handling, and ABCA1-dependent export rather than on total cellular cholesterol alone. Although several regulator-specific mechanisms remain preclinical and await independent replication, this review integrates these pathways and discusses their nutritional and translational relevance in type 2 diabetes."

Journal • Review • Diabetes • Dyslipidemia • Metabolic Disorders • Oncology • Type 2 Diabetes Mellitus • ABCA1 • ABCG1 • APOA1 • IGF1 • MIR33A • TNFA

Anti-Inflammatory Effects of Pemafibrate Are Associated with Improved Endothelial Function Beyond Triglyceride Lowering: Insights from the PRIME Trial (AHA 2026) - "Abstract is embargoed at this time."

Cardiovascular • Peripheral Arterial Disease

Neuroprotective Effect of Oral Pemafibrate with Suppression of p-ULK1 Elevation in a Rat Ocular Hypertension-Induced Glaucoma Model. (PubMed, Curr Eye Res) - "These results suggest that pemafibrate may have neuroprotective effects associated with suppression of OHT-induced p-ULK1 Ser757 elevation. Because autophagic flux was not directly measured, the present findings suggest a possible modulatory role in autophagy-related signaling rather than demonstrating restoration of autophagy function."

Journal • Preclinical • Cardiovascular • Dyslipidemia • Glaucoma • Ophthalmology • PPARA • ULK1

Selective Pharmacological Activation of PPARα/δ/γ Alters the Triglyceride Composition of Fatty Liver in a Diet-Induced MASLD Mouse Model. (PubMed, Biomolecules) - "We determined the effects of PPARα/δ/γ subtype-selective agonists (pemafibrate, seladelpar, and pioglitazone, respectively) on the hepatic triglyceride (TG) profile using LC-MS in a MASLD mouse model established by administering a high-fat/high-cholesterol/high-cholic acid (HFCC) diet combined with cyclodextrin-containing water, which is thought to induce fatty liver over a short period. Pioglitazone reduced the relative total TG signal by 44%, which included a decrease in the proportion of polyunsaturated fatty acid-rich TG54 and an increase in the proportion of TG58/TG56 with 1-3 unsaturated bonds. We are the first to demonstrate that selective activation of PPARα/δ/γ has different effects on the TG profile in fatty liver."

Journal • Preclinical • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • PPARA

Study to Evaluate the Efficacy and Safety of K-808 (Pemafibrate) in Participants With Primary Biliary Cholangitis (PBC) With Inadequate Response to Ursodeoxycholic Acid (UDCA) and/or Obeticholic Acid (OCA) Treatment. (clinicaltrials.gov) - P2 | N=46 | Completed | Sponsor: Kowa Research Institute, Inc. | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Immunology • Primary Biliary Cholangitis

Methodological Considerations in the Interpretation of Non-invasive Surrogate Markers in a Post Hoc Analysis of Pemafibrate in Metabolic Dysfunction-associated Steatotic Liver Disease. (PubMed, J Clin Exp Hepatol) - No abstract available

Journal • Retrospective data • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease

Discordance between remnant cholesterol and small dense LDL cholesterol obscures interpretation of the results of the PROMINENT trial. (PubMed, J Clin Lipidol) - "Conventional lipid biomarkers primarily describe static concentrations and may not adequately distinguish remnant persistence from downstream remodeling. A kinetic interpretation of triglyceride-rich lipoprotein metabolism may improve biomarker assessment and cardiovascular risk stratification."

Journal • Cardiovascular • Dyslipidemia • APOB

Serum Metabolomics Reveals Carnitine Metabolism as a Possible Central Metabolic Axis of Pemafibrate Action. (PubMed, Int J Mol Sci) - "Mechanistically, PEM did not significantly alter genes involved in carnitine biosynthesis or transport, but upregulated hepatic carnitine O-acetyltransferase and carnitine O-octanoyltransferase, key enzymes of carnitine utilization and turnover. Collectively, these findings suggest that enhanced carnitine metabolism represents an important metabolic axis of PEM action."

Journal • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders

ALT Reduction Following Pemafibrate Treatment in MASLD and MetALD with Dyslipidemia: Associations with the Baseline Liver Enzyme Levels. (PubMed, Intern Med) - "The findings in the small MetALD subgroup were exploratory. Baseline ALT, AST, and GGT levels were correlated with ALT reduction, but none were independent predictors in the multivariable model."

Journal • Addiction (Opioid and Alcohol) • Dyslipidemia • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Pemafibrate is associated with greater reductions in MDA-LDL and small dense LDL fractions with exploratory PBMC gene-expression changes: a prespecified subanalysis of the PARADISE in Kagoshima study. (PubMed, Front Clin Diabetes Healthc) - "These findings suggest modification of selected lipid-quality biomarkers. Their clinical relevance remains to be established."

Journal • Atherosclerosis • Cardiovascular • Diabetes • Dyslipidemia • Hypertriglyceridemia • Metabolic Disorders • Type 2 Diabetes Mellitus • ABCA1 • PPARA

Pemafibrate Improves Cholestatic Markers Regardless of the Presence of Primary Biliary Cholangitis. (PubMed, Hepatol Res) - P3 | "Pemafibrate improved cholestatic markers in a baseline-dependent manner, regardless of the presence of PBC, suggesting mechanisms beyond PBC-specific pathology. These findings support a broader anti-cholestatic effect, potentially mediated by coordinated modulation of bile acid metabolism and immunological activity through PPARα activation."

Journal • Cholestasis • Dyslipidemia • Hepatology • Hypertriglyceridemia • Immunology • Primary Biliary Cholangitis • FGF19 • FGF21 • PPARA

A One-Year Retrospective Observational Study Reveals the Transient Nature of Pemafibrate-Induced LDL-C Elevation: Implications Beyond the PROMINENT Trial. (PubMed, Drug Des Devel Ther) - "LDL-C elevation peaks at approximately 3 months and returns to baseline by one year, indicating that the increase is temporary rather than persistent. These findings refine the understanding of pemafibrate's lipid effects and support its long-term safety profile."

Journal • Observational data • Retrospective data • Dyslipidemia • Hypertriglyceridemia

A Post-Marketing Clinical Trial of Pemafibrate in Patients ?ith Hypercholesterolemia and Inadequate Response to Statins (clinicaltrials.gov) - P4 | N=120 | Recruiting | Sponsor: Kowa Company, Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Dyslipidemia • Familial Hypercholesterolemia • Metabolic Disorders

Efficacy and Safety of Pemafibrate for the Treatment of Dyslipidaemia: A Meta-Analysis. (PubMed, J Coll Physicians Surg Pak) - "Pemafibrate is an effective and well-tolerated option for dyslipidaemia management, particularly in patients with hypertriglyceridaemia. Key Words: Pemafibrate, Dyslipidaemia, Triglyceride, Efficacy, Safety."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Dyslipidemia • PPARA

Data Mining of the Japanese Adverse Drug Event Report Database and Animal Experiments for Assessment of Risks Associated With Pemafibrate. (PubMed, In Vivo) - "The JADER analysis suggests that pemafibrate may be a safer alternative to conventional fibrates, with a potentially lower association with rhabdomyolysis and acute renal failure, even when co-administered with statins. Preclinical animal experiments support the results of the JADER analysis. However, large-scale prospective studies are needed to clarify the risks of pemafibrate."

Adverse events • Journal • Acute Kidney Injury • Renal Disease

A case of lipoprotein glomerulopathy in which complete remission was achieved by pemafibrate therapy. (PubMed, CEN Case Rep) - "To our knowledge, this is the first documented case of complete remission of proteinuria induced by pemafibrate in a patient with LPG. Pemafibrate may be a promising targeted therapy for this rare glomerular disorder."

Journal • Dyslipidemia • Glomerulonephritis • Metabolic Disorders • Renal Disease • APOE • PPARA

Current status of tamoxifen-related drug-induced liver injury at our hospital (JBCS 2026) - "TAM was discontinued in all cases, and pemafibrate treatment was initiated in 3 cases...On the other hand, there were also cases with only minor changes in hepatobiliary enzymes and imaging, requiring careful attention. Careful consideration of patient benefit is necessary when deciding whether to continue or discontinue TAM, and it is considered important to establish a monitoring system that includes regular liver function and imaging evaluations."

Clinical • Breast Cancer • Diabetes • Fibrosis • Genetic Disorders • Hepatology • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Hypertension • Immunology • Infectious Disease • Liver Failure • Metabolic Disorders • Obesity • Solid Tumor • Type 2 Diabetes Mellitus

Beyond the GH-IGF-1 Axis: A Network Perspective Integrating Clinical Observations and Mechanistic Insights. (PubMed, Endocr Connect) - "Case 1 involved acromegaly improved by the peroxisome proliferator-activated receptor-α (PPAR-α) agonist pemafibrate. Case 2 involved Prader-Willi syndrome (PWS) with severe obesity treated using dulaglutide...In Case 3, behavioral therapy stabilized metabolic deterioration in a patient with a body mass index of 50.7 kg/m2, even though GH and IGF-1 levels remained low after weight reduction, suggesting mechanisms independent of the GH-IGF-1 axis. These findings support a conceptual shift from a linear GH-IGF-1 axis to an integrated GH-IGF-1 network that connects peripheral signals, hypothalamic regulation, and higher brain functions, offering a novel framework for personalized obesity management."

Journal • Acromegaly • Endocrine Disorders • Genetic Disorders • Obesity • Prader–Willi syndrome • IGF1

Comparative Cardiovascular, Lipid, and Safety Effects of Lipid-Modifying Therapies in Diabetes: An Agent-, Class-, and Dose-Level Network Meta-Analysis. (PubMed, Cardiovasc Drugs Ther) - "Lipid-modifying therapies were associated with beneficial and specific cardiovascular and lipid effects in diabetes. The results provide more granular and tailored lipid management strategies."

Journal • Retrospective data • Review • Cardiovascular • Diabetes • Metabolic Disorders • Myocardial Infarction

The effect of Pemafibrate on glucose metabolism and FGF21: a systematic review and meta-analysisa of randomized controlled trials. (PubMed, Eur J Clin Pharmacol) - "Pemafibrate significantly improves glucose metabolism, insulin sensitivity, and increases FGF21 levels, making it a promising therapeutic option for patients with metabolic disorders."

Clinical • Journal • Retrospective data • Review • Metabolic Disorders • FGF21 • PPARA

A Case of Familial Chylomicronemia Syndrome Caused by a Novel Homozygous GPIHBP1 Mutation Successfully Treated with the Selective PPARα Modulator Pemafibrate. (PubMed, J Atheroscler Thromb) - "We report an extremely rare case of FCS caused by a novel homozygous mutation in the GPIHBP1 gene, in which pregnancy served as a major trigger for severe hypertriglyceridemia. Early diagnosis and strict lipid control are essential to prevent recurrent pancreatitis in patients with GPIHBP1 deficiency."

Journal • Dyslipidemia • Familial Chylomicronemia Syndrome • Hypertriglyceridemia • Metabolic Disorders • Pain • Pancreatitis • Rare Diseases • Severe Hypertriglyceridemia • FEN1 • GPI • LPL • PPARA