Type 2 diabetes mellitus is a metabolic disorder where disease progression is characterized by peripheral tissue insulin resistance, hyperglycemia, islet β-cell compensation, hyperinsulinemia, dyslipidemia, increased liver gluconeogenesis and ultimate loss of β-cell mass and function.  In particular, there is significant unmet medical need for new agents that delay disease progression by improving glycemic control and β-cell mass and function.

Glucagon-like peptide-1 (GLP-1) is a member of the incretin family of neuroendocrine peptide hormones secreted from L-cells of the intestine in response to food ingestion. GLP-1 has multiple metabolic effects that are attractive for an anti-diabetic agent.  A key function of GLP-1 is to activate its receptor, GLP-1R, on the pancreatic β-cell to enhance glucose-dependent insulin secretion.  Additional positive metabolic benefits of GLP-1 include suppression of excessive glucagon production, decreased food intake, delayed gastric emptying and improvement of β-cell mass and function. Unfortunately, the rapid proteolysis of GLP-1 in blood limits its use as a therapeutic agent.

TTP054 has been identified as an orally bioavailable, potent, non-peptide agonist of GLP-1R for the treatment of type 2 diabetes. TTP054 is anticipated to provide excellent glycemic control and an attractive safety profile for the treatment of type 2 diabetes.  
   
TTP054 is presently in phase Ib/IIa clinical studies assessing its modulation of glycemic indices in patients with type 2 diabetes.