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.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: 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.

Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics

“…Type II diabetes mellitus is a metabolic disorder of deranged fat, protein and carbohydrate metabolism resulting in hyperglycaemia from insulin resistance and inadequate insulin secretion [ 152 ]. This condition is very difficult to treat and even in countries like the USA, fewer than 50% of patients achieve the HbA1c goal of < 7% set by the American Diabetes Association [ 152 , 153 ]. One of the reasons might be poor adherence to treatment regimes [ 154 - 156 ], as well as poor diet and knowledge regarding nutrition [ 157 ].…”

Novel approaches to the treatment of hyperglycaemia in type 2 diabetes mellitus

“…The enzyme glucokinase (GK) acts in β‐cells and hepatocytes as a glucose sensor to stimulate insulin secretion and regulate hepatic gluconeogenesis, glycolysis, glycogen synthesis, lipogenesis and glucose oxidation. GK activators are small molecules that have been studied in humans, with promising glucose‐lowering effects; however, concerns about potential side‐effects including hypoglycaemia, hyperlipidaemia and hepatic steatosis may limit further development of this class of AHA …”

Antidiabetic Effect of Tibetan Medicine Tang-Kang-Fu-San in db/db Mice via Activation of PI3K/Akt and AMPK Pathways

“…Diabetes mellitus (DM) is a well-known group of metabolic disorders characterized by hyperglycemia being resulted from abnormal insulin secretion and/or action ( Rochester and Akiyode, 2014 ). DM affects millions of people worldwide, with a rapidly increasing incidence and prevalence.…”

“…DM affects millions of people worldwide, with a rapidly increasing incidence and prevalence. According to the International Diabetes Federation’s statistics in 2013, 382 million people worldwide have diabetes, more than 90% of them have type 2 diabetes (T2DM), and even this number will increase to 592 million by 2035 ( Rochester and Akiyode, 2014 ; Saisho, 2015 ). Insulin resistance (IR) occurs when the insulin-sensitive tissues (mainly skeletal muscle, adipose tissue, and liver) lose their ability to respond properly to insulin ( Hirabara et al, 2012 ), which has been assumed as a major pathophysiological feature of T2DM ( Brunetti et al, 2014 ; Saisho, 2015 ).…”