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
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
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
Phase 1 PK and safety combination study to start H2 2016