Pemafibrate, a New Selective PPAR α Modulator: Drug Concept and Its Clinical Applications for Dyslipidemia and Metabolic Diseases

AbstractPurpose of ReviewReduction of serum low-density lipoprotein cholesterol (LDL-C) levels by statins, ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has been shown to significantly reduce cardiovascular events risk. However, fasting and postprandial hypertriglyceridemia as well as reduced high-density lipoprotein cholesterol (HDL-C) remain as residual risk factors of atherosclerotic cardiovascular diseases (ASCVD). To treat patients with hypertriglyceridemia and/or low HDL-C, drugs such as fibrates, nicotinic acids, and n-3 polyunsaturated fatty acids have been used. However, fibrates were demonstrated to cause side effects such as liver dysfunction and increase in creatinine levels, and thus large-scale clinical trials of fibrates have shown negative results for prevention of ASCVD. The failure could be attributed to their low selectivity and potency for binding to peroxisome proliferator-activated receptor (PPAR) α. To resolve these issues, the concept of selective PPARα modulator (SPPARMα) with a superior balance of efficacy and safety has been proposed and pemafibrate (K-877) has been developed.Recent FindingsPemafibrate, one of SPPARMs α, was synthesized by Kowa Company, Ltd. for better efficiency and safety. Clinical trials in Japan have established the superiority of pemafibrate on effects on serum triglycerides (TG) reduction and HDL-C elevation as well safety. Although available fibrates showed worsening of...
Source: Current Atherosclerosis Reports - Category: Cardiology Source Type: research

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Abstract Diabetic dyslipidemia is a common condition in patients with Type 2 diabetes mellitus (T2DM). However, with the increasing application of statins which mainly decrease low-density lipoprotein cholesterol (LDL-C) levels, clinical trials and meta-analysis showed a clearly increase of the incidence of new-onset DMs, partly due to genetic factors. To determine whether a causal relationship exists between LDL-C and T2DM, we conducted a two-sample Mendelian Randomization (MR) analysis using genetic variations as instrumental variables (IVs). Initially, 29 SNPs significantly related to LDL-C (P≤ 5.0×10-...
Source: Aging - Category: Biomedical Science Authors: Tags: Aging (Albany NY) Source Type: research
(Natural News) If you’ve ever suspected that certain medical treatments seem to be trading one problem for another, you may be onto something. Case in point: A recent study revealed that people who take statins in hopes of reducing their risk of cardiovascular events could be raising their risk of diabetes in the process. In...
Source: - Category: Consumer Health News Source Type: news
CONCLUSION: Pharmaceutical approach of CVD in T2DM is multilevel and complex. Drug classes featuring pleiotropic effects may boost our armamentarium in the fight against CVD. PMID: 32013815 [PubMed - in process]
Source: Current Vascular Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Curr Vasc Pharmacol Source Type: research
Analysis of raw individual patient level data gives more accurate picture of drug ’s link to heart problems Related items fromOnMedica People on statins at greater risk of skin infections and diabetes Adding insulin to metformin linked to higher mortality Vitamin D does not reduce kidney damage in type 2 diabetes Raised risk of MI and mortality when starting sulfonylurea Use of DPP-4 inhibitors associated with increased risk of IBD
Source: OnMedica Latest News - Category: UK Health Source Type: news
Fight Aging! publishes news and commentary relevant to the goal of ending all age-related disease, to be achieved by bringing the mechanisms of aging under the control of modern medicine. This weekly newsletter is sent to thousands of interested subscribers. To subscribe or unsubscribe from the newsletter, please visit: Longevity Industry Consulting Services Reason, the founder of Fight Aging! and Repair Biotechnologies, offers strategic consulting services to investors, entrepreneurs, and others interested in the longevity industry and its complexities. To find out m...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
CONCLUSIONS: The clinical polymorphism effectiveness outlined therein will be assured by diagnostic improvements suitable for driving treatment decisions. In light of our experimental results and literature data, the analysis of the SLCO1B1 T521C variant will allow clinicians to take advantage from a better treatment planned for their patients in order to minimize neuromuscular pain and maximize benefits. PMID: 31957862 [PubMed - in process]
Source: European Review for Medical and Pharmacological Sciences - Category: Drugs & Pharmacology Tags: Eur Rev Med Pharmacol Sci Source Type: research
This study systematically reviewed and summarized earlier findings from randomized clinical trials about the effects of statins on serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6 in patients with abnormal glucose homeostasis. METHODS: Relevant articles published through October 2019 were searched using suitable key words on the PubMed/MEDLINE, SCOPUS, EMBASE, and Google Scholar databases. RCTs were included if they compared the effects of statins on serum concentrations of CRP and IL-6 in adults with abnormal glucose homeostasis. The effect sizes were represented as weighted mean differences (W...
Source: Clinical Therapeutics - Category: Drugs & Pharmacology Authors: Tags: Clin Ther Source Type: research
Although the improved control of hyperglycaemia and other cardiovascular risk factors was associated with a parallel decline of atherosclerotic cardiovascular disease (ASCVD) and death in both type 1 (T1) and type 2 (T2) diabetes mellitus (DM), the burden of death and hospitalization for ASCVD remains significantly higher by about 2-fold versus the matched non-DM population. Life style interventions, such as physical activity and healthy diet, and drugs, such as statins and low-dose aspirin, may have beneficial effects by targeting one or multiple pathways responsible for accelerated atherosclerosis and its thrombotic complications.
Source: Diabetes Research and Clinical Practice - Category: Endocrinology Authors: Source Type: research
CONCLUSIONS: Intervention response heterogeneity was significant for nonfatal MI. Response heterogeneity may need consideration in a CVD-outcome trial design. PMID: 31898874 [PubMed - as supplied by publisher]
Source: Obesity - Category: Eating Disorders & Weight Management Authors: Tags: Obesity (Silver Spring) Source Type: research
AbstractObesity and diabetes can lead to heart failure with preserved ejection fraction (HFpEF), potentially because they both cause expansion and inflammation of epicardial adipose tissue and thus lead to microvascular dysfunction and fibrosis of the underlying left ventricle. The same process also causes an atrial myopathy, which is clinically evident as atrial fibrillation (AF); thus, AF may be the first manifestation of HFpEF. Many patients with apparently isolated AF have latent HFpEF or subsequently develop HFpEF. Most patients with obesity or diabetes who have AF and exercise intolerance have increased left atrial p...
Source: European Journal of Heart Failure - Category: Cardiology Authors: Tags: Review Source Type: research
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