Non-insulin dependent diabetes mellitus: present therapies and new drug targets.
Type 2 Diabetes Mellitus (DM) or Non-Insulin Dependent Diabetes Mellitus (NIDDM) accounts for 90-95% of all diabetes cases and has become a major health concern over the years. This disease has assumed frightening proportions due to unhealthy food habits and sedentary life style. About a decade ago, due to the absence of defined molecular targets or an understanding of disease pathophysiology, treatment of this disease was mostly focused on insulin secretion or administration of external insulin. During the past decade however, advent of genomics and proteomics has helped in understanding the molecular alteration characteristics of NIDDM. Untreated type 2 diabetes leads to several complications such as hyperlipidemia, hypertension and atherosclerosis--collectively known as Syndrome X. Though United Kingdom Prospective Diabetes Study (UKPDS) showed that normalization of hyperglycemia could prevent majority of diabetes complications, the available treatment regime does not adequately normalize the blood glucose level in type 2 diabetic patients. Currently, four distinct classes of oral hypoglycemic agents are available, some of which can act as lipid lowering agents as well. The efficacy and side effect profiles of these drugs are still to be optimized, so there is an unmet need for better candidates. Several new targets as well as better drugs for old targets are under investigation across the world. Availability of such drugs, based on the validated targets, may lead to a new therapeutic paradigm for the prevention of diabetes as well as complications arising out of it. The current review will deal with existing oral therapies for type 2 diabetes as well as the emerging therapeutic targets.
Das
Saibal Kumar
SK
Metabolic Disorders Group, Dr. Reddy's Laboratories Ltd., Discovery Research, Bollaram Road, Miyapur, Hyderabad 500049, India. saibalkumardas@drreddys.com
Chakrabarti
Ranjan
R
D055372:AMP-Activated Protein Kinases; D058667:Adrenergic beta-3 Receptor Agonists; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects
D058667:Adrenergic beta-3 Receptor Agonists; D007004:Hypoglycemic Agents; D007328:Insulin; D009097:Multienzyme Complexes; D011972:Receptor, Insulin; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose