GLP-1 based therapy for type 2 diabetes.
Type 2 diabetes mellitus is a major and growing health problem throughout the world. Current treatment approaches include diet, exercise, and a variety of pharmacological agents including insulin, biguanides, sulfonylureas and thiazolidinediones. New therapies are still needed to control metabolic abnormalities, and also to preserve beta-cell mass and to prevent loss of beta-cell function. Glucagon-like peptide 1 (GLP-1) is a drug candidate which potentially fulfils these conditions. GLP-1 is an incretin hormone secreted by intestinal L-cells in response to meal ingestion is a novel pharmacological target with multiple antihyperglycemic actions. GLP-1 glucoregulatory actions include glucose-dependent enhancement of insulin secretion, inhibition of glucagon secretion, slowing of gastric emptying and reduction of food intake. GLP-1 is rapidly inactivated by amino peptidase, dipeptidyl peptidase IV (DPP-IV) and the utility of DPP-IV inhibitors are also under investigation. There is a recent upsurge in the development of GLP-1 mimetics and DPP-IV inhibitors as potential therapy for type 2 diabetes. However, both the strategies are having their own advantages and limitations. The present review summarizes the concepts of GLP-1 based therapy for type 2 diabetes and the current preclinical and clinical development in GLP-1 mimetics and DPP-IV inhibitors. Further, the potential advantages and the limitations of both the strategies are discussed.
Department of Pharmacology, New Chemical Entity Research, Lupin Research Park, Village Nande, Taluk Mulshi, Pune 411042, Maharashtra, India. adk_bits@yahoo.com
D K
DK
Arulmozhi
B
B
Portha
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000503:physiopathology*; D018819:Dipeptidyl Peptidase 4 / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018027:Receptors, Glucagon / Q000819:agonists
C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D007004:Hypoglycemic Agents; D011480:Protease Inhibitors; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D018819:Dipeptidyl Peptidase 4