Type 2 Diabetes

Type 2 diabetes is a common metabolic disorder of high blood glucose associated with insulin resistance. It is differentiated from type 1 diabetes in which the primary defect is the inability of the pancreas to produce insulin. Patients with type 2 diabetes often require medication to maintain glucose homeostasis. Given the rise in the incidence of obesity and sedentary lifestyle, the incidence of type 2 diabetes has reached epidemic proportions. Despite available therapies, such as metformin, sulfonylureas, thiazolidinediones, incretin mimetics, and other therapies, an unmet medical need for safe and convenient treatments persists.

For decades the presence of systemic markers of inflammation has been known to increase with obesity. The adipose tissue has been shown to express multiple inflammatory cytokines, including TNF-α, IL-6, and the CCR2 chemokine MCP-1, the expression levels of which correlate with the degree of adiposity. Several of these mediators, including MCP-1 (also called chemokine ligand 2 (CCL2)), the main ligand for CCR2, have been shown to impair insulin sensitivity in adipose tissue, skeletal muscle and liver. MCP-1 impairs insulin-stimulated glucose uptake in human adipocytes and skeletal muscle cells, providing a link between inflamed adipose tissue and insulin resistance.

CCX140 is being developed as an orally delivered therapy for the treatment of patients with type 2 diabetes. Single-ascending and multiple-ascending dose Phase I studies of CCX140 in healthy volunteers have been conducted. A Phase II trial in type 2 diabetes is anticipated to start in Q1 2010.

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