XBiotech has concluded a Phase II pilot study to test MABp1 in patients with Type 2 diabetes. The study was headed by world-leading diabetes expert Dr. Marc Donath, Head of Endocrinology, Diabetes and Metabolism at University Hospital of Basel, Switzerland. Remarkable findings in this study have provided the basis to advance clinical programs in Type 2 diabetes.
Type 2 diabetes is one of the fastest growing and most significant disease burdens among industrialized societies. New treatment options are needed to prevent progression of disease and loss of pancreatic function in type 2 diabetic patients.
In type 2 diabetes, systemic inflammation, including infiltration of inflammatory cells into white adipose tissue and the pancreas, likely plays a role in the development of insulin resistance and loss of insulin production, respectively. Chronic (sterile) inflammation present in the adipose tissue is thought to reduce sensitivity of these fat storage cells to insulin. Insulin responsiveness in adipose tissue is however necessary to trigger adipose cells to take up sugar from the blood. When inflammation makes them insensitive to insulin, they can no longer efficiently take up sugar, and thus the control of blood sugar levels can be difficult.
The pancreas is able to compensate for reduced insulin sensitivity by increasing output of insulin. Eventually, however, the pancreas may be unable to keep up with insulin demand. The increased load on the pancreas results in stress of the pancreas and an inflammatory process can ensue in the pancreas itself. This inflammation may contribute to loss of function in the pancreas, exacerbating the disease process. Eventually, inflammatory processes in the pancreas can lead to a collapse of insulin production and insulin dependence.
Numerous drugs have been approved to treat type 2 diabetes. None, however, address the underlying disease process. Linagliptin for example, inhibits an enzyme that in turn regulates levels of two hormones (GLP-1 & GIP) involved in stimulating the pancreas to produce insulin. Linagliptin’s action to increase GLP-1 and GIP activity is indeed effective at hyperstimulating the pancreas to produce insulin. However, by working the pancreas harder, further stress is put on an already stressed pancreas. The occurrence of pancreatitis (acute inflammation of the pancreas) in patients treated with these agents is evidence of this problem.
The mechanism of action of XBiotech’s antibody therapy—to reduce inflammation that compromises pancreas function and glycemic control—could enhance glycemic control by improving the overall status of the systemic inflammatory condition present in type 2 diabetics. This represents a breakthrough in management of the disease.
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