Novel and emerging diabetes mellitus drug therapies for the type 2 diabetes patient

Abstract

Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia as a result of insulin resistance and inadequate insulin secretion. Although a wide variety of diabetes therapies is available, yet limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit their use. In addition, many patients in the United States fail to meet the therapeutic HbA1c goal of < 7% set by the American Diabetes Association. As such new and emerging diabetes therapies with different mechanisms of action hope to address some of these drawbacks to improve the patient with type 2 diabetes. This article reviews new and emerging classes, including the sodium-glucose cotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors; protein tyrosine phosphatase 1B inhibitors, G Protein-Coupled receptor agonists and glucokinase activators. These emerging diabetes agents hold the promise of providing benefit of glucose lowering, weight reduction, low hypoglycemia risk, improve insulin sensitivity, pancreatic β cell preservation, and oral formulation availability. However, further studies are needed to evaluate their safety profile, cardiovascular effects, and efficacy durability in order to determine their role in type 2 diabetes management.

Keywords: Type 2 diabetes mellitus; Sodium dependent glucose co-transporter 2 inhibitors; 11β-Hydroxysteroid dehydrogenase type 1 inhibitors; Glycogen phosphorylase inhibitors; Protein tyrosine phosphatase 1B inhibitors; G protein-coupled receptor agonists; Glucokinase activators

Core tip: Type 2 diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycemia. Limited efficacy, adverse effects, cost, contraindications, renal dosage adjustments, inflexible dosing schedules and weight gain significantly limit the use of currently available anti-hyperglycemic agents. In the past, drug researchers targeted defects of pancreatic β-cell failure and insulin resistance, but more recent attention has shifted to other contributing factors. This article reviews new and emerging diabetes classes, including the sodium-glucose cotransporter-2 inhibitors, 11β-Hydroxysteroid dehydrogenase type 1 inhibitors, glycogen phosphorylase inhibitors, protein tyrosine phosphatase 1B inhibitors, G protein-coupled receptor agonists, and glucokinase activators.