Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator for management of atherogenic dyslipidaemia.

Authors:
Jean-Charles Fruchart
Jean-Charles Fruchart
Université Lille 2
France

Cardiovasc Diabetol 2017 10 4;16(1):124. Epub 2017 Oct 4.

R3i Foundation, St. Alban-Anlage 46, Basel, Switzerland.

Despite best evidence-based treatment including statins, residual cardiovascular risk poses a major challenge for clinicians in the twenty first century. Atherogenic dyslipidaemia, in particular elevated triglycerides, a marker for increased triglyceride-rich lipoproteins and their remnants, is an important contributor to lipid-related residual risk, especially in insulin resistant conditions such as type 2 diabetes mellitus. Current therapeutic options include peroxisome proliferator-activated receptor alpha (PPARα) agonists, (fibrates), but these have low potency and limited selectivity for PPARα. Modulating the unique receptor-cofactor binding profile to identify the most potent molecules that induce PPARα-mediated beneficial effects, while at the same time avoiding unwanted side effects, offers a new therapeutic approach and provides the rationale for development of pemafibrate (K-877, Parmodia™), a novel selective PPARα modulator (SPPARMα). In clinical trials, pemafibrate either as monotherapy or as add-on to statin therapy was effective in managing atherogenic dyslipidaemia, with marked reduction of triglycerides, remnant cholesterol and apolipoprotein CIII. Pemafibrate also increased serum fibroblast growth factor 21, implicated in metabolic homeostasis. There were no clinically meaningful adverse effects on hepatic or renal function, including no relevant serum creatinine elevation. A major outcomes study, PROMINENT, will provide definitive evaluation of the role of pemafibrate for management of residual cardiovascular risk in type 2 diabetes patients with atherogenic dyslipidaemia despite statin therapy.

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12933-017-0602-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5628452PMC

Still can't find the full text of the article?

We can help you send a request to the authors directly.
October 2017
35 Reads

Publication Analysis

Top Keywords

atherogenic dyslipidaemia
16
peroxisome proliferator-activated
8
dyslipidaemia despite
8
residual cardiovascular
8
proliferator-activated receptor
8
type diabetes
8
novel selective
8
pemafibrate k-877
8
cardiovascular risk
8
statin therapy
8
receptor alpha
8
pemafibrate
5
development pemafibrate
4
offers therapeutic
4
therapeutic approach
4
approach rationale
4
rationale development
4
k-877 parmodia™
4
modulator spparmα
4
monotherapy add-on
4

References

(Supplied by CrossRef)
Article in Lancet Diabetes Endocrinol.
The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration et al.
Lancet Diabetes Endocrinol. 2014
Article in Obes Rev
LS Adair et al.
Obes Rev 2014
Article in J Am Coll Cardiol
NJ Stone et al.
J Am Coll Cardiol 2014
Article in Eur Heart J
AL Catapano et al.
Eur Heart J 2016
Article in Lancet
J Fulcher et al.
Lancet 2015
Article in N Engl J Med
CP Cannon et al.
N Engl J Med 2015
Article in N Engl J Med
MS Sabatine et al.
N Engl J Med 2017
Article in Cardiovasc Diabetol.
JC Fruchart et al.
Cardiovasc Diabetol. 2013
Article in Atherosclerosis.
Ž Reiner et al.
Atherosclerosis. 2013
Article in Cardiovasc Diabetol.
P Valensi et al.
Cardiovasc Diabetol. 2016
Article in N Engl J Med
PJ Barter et al.
N Engl J Med 2007

Similar Publications