Evoglipitin

Evogliptin is an orally bioavailable, selective dipeptidyl peptidase-4 (DPP-4) inhibitor.

DPP-4 inhibitors control glucose levels by preventing the breakdown of the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), which stimulate insulin secretion in response to the increased levels of glucose in the period following meals. In October 2015, SUGANON® (evogliptin, 5mg) received its first global approval in the Republic of Korea for blood glucose control in patients with type-2 diabetes mellitus. Evogliptin is not approved by the FDA.

Mechanism of Action

Systemic Effects

DPP-4 inhibition results in GLP-1 mediated hypoglycemia and other beneficial effects relevant to the NASH population including:

  • Delayed gastric emptying
  • Increased satiety
  • Increased glucose-dependent insulin secretion
  • Decreased glucagon secretion
  • Improved beta cell function

Liver Specific

DPP-4 is highly expressed in the liver and plays a direct role in:

  • Regulation of hepatic gluconeogenesis
  • Regulation of lipid metabolism

In NASH, increased DPP-4 serum levels and hepatic DPP-4 expression is correlated with disease severity.

In preclinical and clinical settings, DPP-4 inhibition has been shown to:

  • Decrease hepatic glucose production
  • Improve hepatic triglyceride content and steatosis
  • Reduce histologic markers of inflammation and ballooning

More Information

Diet-Induced Adipose Tissue Inflammation and Liver Steatosis Are Prevented by DPP-4 Inhibition in Diabetic Mice

Sitagliptin attenuates methionine/choline-deficient diet-induced steatohepatitis

Dipeptidyl peptidase IV (DDP IV) in NASH patients

Evogliptin: a new dipeptidyl peptidase inhibitor for the treatment of type 2 diabetes

Hepatic role in an early glucose-lowering effect by a novel dipeptidyl peptidase 4 inhibitor, evogliptin, in a rodent model of type 2 diabetes

Clinical Trials

Phase 1 PK and safety combination study to start H2 2016

EVO for NASH

In combination with CVC

Stage

Pre-clinical

Prevalence

3-5% of US population