Elafibranor (GFT505) is an agonist of the peroxisome proliferator-activated receptor-α (PPAR-α) and peroxisome proliferator-activated receptor-δ (PPAR-δ) with EC50 values of 45 and 175 nM, respectively.

PPARδ:175 nM (EC50), PPARα:45 nM (EC50)

GFT505, under development as a dual PPAR-α/δ agonist, targets both Type 2 Diabetes Mellitus (T2DM) and non-alcoholic fatty liver disease. It, alongside its active metabolite GFT1007, exhibits strong agonistic activity for PPAR-α and, to a lesser extent, PPAR-δ.

GFT505 improves insulin sensitivity and early studies indicate it may be useful in non-alcoholic fatty liver disease which is being tested in a Phase IIb study. Elafibranor is well tolerated and does not cause weight gain or cardiac events, but does produce a mild, reversible increase in serum creatinine. Elafibranor improves insulin sensitivity, glucose homeostasis, and lipid metabolism and reduces inflammation. GFT505 treatment improves glucose control and plasma lipids in diabetic db/db mice. A significant dose-dependent reduction of hepatic expression of the key gluconeogenic enzymes glucose 6-phosphatase (G6Pase), PEPCK, and fructose 1,6-bisphosphatase 1 (FBP1) is observed with GFT505. GFT505 does not induce cardiac adverse effects of PPARγ-activating agonists in monkeys