Suganon Mechanism of Action

Anti-Diabetic (DPP-4 inhibitor).
Pharmacology: Pharmacodynamics: Evogliptin is a member of a class of oral anti-hyperglycaemic agents called DPP-4 inhibitors. Evogliptin selectively inhibits the activity of DPP-4 by reversibly binding to DPP-4, an enzyme that inactivates incretin hormones such as GLP-1 (Glucagon-like peptide-1). Evogliptin dose-dependently inhibits the activity of DPP-4, thereby blocking GLP-1 from being inactivated by DPP-4, increasing the concentration of endogenous active GLP-1 and prolonging its action, and improves glucose-dependent insulin secretion in pancreatic beta cells by GLP- 1, and suppresses increase in blood sugar. The IC₅₀ of evogliptin against recombinant human DPP-4 was 0.980 nM, and the inhibitory constant (K_i) was 0.525 nM. Compared to DPP-8 and DPP-9, evogliptin showed high selectivity of about 7,898 times and about 6,058 times, respectively, to DPP-4 (in vitro).
Pharmacokinetics: Absorption: After a single oral administration of evogliptin 5mg in fasting state, the maximum blood concentration reached in about 4 hours. In repeated oral administration, steady state reached in 48 hours after the first administration. Comparing the bioavailability of evogliptin 10 mg between fast state and fed state (high-fat meal), it was found that there is no food effect in terms of bioavailability of evogliptin.
Distribution: Evogliptin is widely distributed to tissues after administration. When reacting evogliptin in heparin-treated plasma of mice, rats, dogs, and humans, the plasma protein binding rates of evogliptin were about 63%, about 25%, about 43%, and about 46%, respectively; binding rates were not related to the concentration of evogliptin in the reacted range (100-1,000 ng/mL). In pregnant female rats and rabbits or lactating rats, the concentration of evogliptin in fetal plasma or milk increased maternal exposure dependently.
Metabolism: Metabolic stability of evogliptin was confirmed in in vitro tests using liver microsomes or hepatocytes. Evogliptin circulates in plasma mainly as parent, and the major metabolites are M16, M8, M7, and M13. The main metabolic pathways were hydroxylation (M7, M8), sulfation (M13) by CYP3A4 and glucuronidation by UGT2B7 (M7 → M16). The major metabolites M16, M8, M7, and M13 were all identified as active forms, but showed at least 110 times lower DPP-4 inhibitory activity compared to the evogliptin parent. Therefore, considering the blood exposure level and inhibitory activity of major metabolites, it is very unlikely that the metabolites will reach effective blood levels.
Excretion: After a single oral administration of evogliptin 5mg in fasting state, the mean half-life (t_½) of elimination was about 32.5 hours. After a single oral administration of [14^C]-evogliptin 5mg in fasting state, 74.9% to 93.9% were excreted through urine and feces, respectively. The average excretion rates in urine and feces were 46.1% and 42.8%, respectively, and the main excretory body was the evogliptin parent.