%0 Journal Article
%T Treatment of Type 2 Diabetes by Free Fatty Acid Receptor Agonists
%A Kenneth R. Watterson
%A Brian D. Hudson
%A Trond Ulven
%A Graeme Milligan
%J Frontiers in Endocrinology
%D 2014
%I Frontiers Media
%R 10.3389/fendo.2014.00137
%X Dietary free fatty acids (FFAs), such as ¦Ø-3 fatty acids, regulate metabolic and anti-inflammatory processes, with many of these effects attributed to FFAs interacting with a family of G protein-coupled receptors. Selective synthetic ligands for free fatty acid receptors (FFA1-4) have consequently been developed as potential treatments for type 2 diabetes (T2D). In particular, clinical studies show that Fasiglifam, an agonist of the long-chain FFA receptor, FFA1, improved glycemic control and reduced HbA1c levels in T2D patients, with a reduced risk of hypoglycemia. However, this ligand was removed from clinical trials due to potential liver toxicity and determining if this is a target or a ligand-specific feature is now of major importance. Pre-clinical studies also show that FFA4 agonism increases insulin sensitivity, induces weight loss, and reduces inflammation and the metabolic and anti-inflammatory effects of short chain fatty acids (SCFAs) are linked with FFA2 and FFA3 activation. In this review, we therefore show that FFA receptor agonism is a potential clinical target for T2D treatment and discuss ongoing drug development programs within industry and academia aimed at improving the safety and effectiveness of these potential treatments.
%K diabetes
%K FFA receptor
%K insulin
%K incretin
%K inflammation
%U http://www.frontiersin.org/Journal/10.3389/fendo.2014.00137/abstract