Alogliptin: a Novel Molecule for Improving Glycemic Control in Type II Diabetes Mellitus

Somsuvra      B. Ghatak; Devang      S. Patel; Neeraj      Shanker; Ambrish      Srivastava; Shrikalp      S. Deshpand; Shital      J. Panchal

Abstract

Type 2 diabetes mellitus causes significant morbidity and mortality on account of its progressive nature and results in considerable burden on healthcare resources. It is characterized by high circulating levels of glucose resulting from insulin resistance and impaired insulin secretion. Current treatment strategies have only limited long-term efficacy and tolerability given the progressive nature of the disease leading to inadequate glycemic control and are also associated with undesirable side effects such as weight gain, hypoglycemia and gastrointestinal distress. In the light of these existing limitations, exploring new treatment targets and new therapies have become the need of the hour at present. The incretin pathway, in particular, glucagon-like peptide (GLP-1), plays an important pathological role in the development of type 2 diabetes mellitus, and treatments targeting the incretin system have recently generated surmount interest. These can mainly be categorized into two broad classes; GLP-1 agonists/analogs (exenatide, liraglutide), and dipeptidyl peptidase- 4 inhibitors (sitagliptin, vildagliptin). The gliptins act by prolonging the action of incretins, the gut hormones which can boost insulin levels. Alogliptin is a potent, highly selective dipeptidyl peptidase-4 inhibitor now undergoing clinical testing to support a new drug application for the treatment of type 2 diabetes. The results of Phase II and Phase III human studies, upon evaluation for clinical efficacy, safety and tolerability in patients with type 2 diabetes, have demonstrated that Alogliptin is effective and well tolerated as a treatment for type 2 diabetes, either as monotherapy or in combination with metformin, thiazolidinediones, sulfonylureas and insulin, with an excellent safety profile.

Keywords: Alogliptin, DPP-4 Inhibitors, Incretin, Plasma glucose, Type II Diabetes mellitus, sulphonylureas, thiazolidinediones, Liraglutide, GlaxoSmithKline, circulating enzymatic activity, non-peptidomimetic, vildagliptin, saxagliptin, AstraZeneca, benzonitrilemonobenzoate, Appetite, Hypoglycaemia, quinazolinone, pharmacokinetic, endopeptidase, triglyceride, pioglitazone alone, voglibose, PHARMACOKINETICS, erythrocytes, predominantly, placebo-controlled, ketoconazole, sulfonylureas, ethnicity, discontinuations, urinalysis, Sitagliptin, metformin, gastrointestinal, therapeutic modalities