At least 170 million people worldwide have diabetes, with a predicted increase to 300 million by 2025. Type 2 diabetes (T2D) constitutes about 85%-95% of all diabetes cases in developed countries and accounts for an even higher percentage in developing countries.
 

Type 2 diabetes is characterized by peripheral insulin resistance in skeletal muscle and adipose tissue, and impaired pancreatic ß-cell function, which when combined, elevate plasma glucose

levels. The disease is most frequently associated with obesity, elevated plasma free fatty acids, triglycerides, and intracellular lipid deposition, suggesting that these lipid abnormalities play a role in the etiology of T2D.
 

Current therapies fail to address the underlying pathophysiology of diabetes, and consequently fail to restore normal control of glucose metabolism. In many cases current agents display poor responder rates and ultimately do not impact the rate of progression of the disease. Unmet medical needs  include more effective diagnosis; agents that slow, stop, and reverse the progression of diabetes and its complications with better safety and tolerability profile; and therapy that aids compliance. 
 

The long-term goal of the Diabetes & Metabolism Disease Area (DA) is to establish Novartis as a leading contributor of novel therapies for the treatment of patients with diabetes and its associated metabolic disorders. Deliverables include (1) agents that impact metabolic disturbances associated with inappropriate deposition of intracellular lipid, leading to the onset and progression of T2D; (2) novel model systems for the study of glucose and lipid metabolism, which allow the dissection of genetic and epigenetic factors contributing to discrete cellular defects in diabetes; (3) targets of future value to the discovery of novel antidiabetic agents; (4) a foundational platform for pharmacogenetic approaches to the diagnosis, treatment, and study of diabetes.

Under the leadership of Tom Hughes, diabetes research is conducted at our institutes in Cambridge, USA, East Hanover, USA and Tsukuba, Japan. 

Valencia JV, Mone M, Zhang J, et al. Gene expression is activated by RAGE Ligands S100b and AGE-BSA. Diabetes 53:743 (2004).

Villhauer E, Brinkman J, Naderi G, et al. 1-[[(3-Hydroxy-1-adamantyl) amino]acetyl]-2-cyano-(S)-pyrrolidine: A Potent, Selective and Orally Bioavailable Dipeptidyl Peptidase IV Inhibitor with Antihyperglycemic Properties. J Med Chem. 46:2774 (2003).

Mitani H, Takimoto M, Hughes TE, et al. Dipeptidyl peptidase IV inhibition improves impaired glucose tolerance in high-fat diet-fed rats: Study using a Fischer 344 rat substrain deficient in its enzyme activity.   Jpn J Pharmacol. 88:442 (2002).

Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. J Clin Endocrinol Metab. 86:3717 (2001).

Starlix® (nateglinide)
Starlix is an oral antidiabetic agent indicated as initial therapy to lower blood glucose in patients with type 2 diabetes (non-insulin dependent diabetes mellitus) whose hyperglycemia cannot be adequately controlled by diet and physical exercise.

LAF237 (type 2 diabetes - Phase III) is an oral DPP4 inhibitor. Inhibition of DPP4 represents a new therapeutic concept: it increases the amount of circulating active GLP-1, a peptide that increases insulin secretion in a glucose-dependent fashion, thereby lowering blood glucose levels.  LAF237 is expected to be the first in a new class of anti-diabetic compounds.