Current therapies and emerging drugs in the pipeline for type 2 diabetes.

Background: Diabetes is a global epidemic that affects 347 million people worldwide and 25.8 million adults in the United States. In 2007, the total estimated cost associated with diabetes in the United States in 2007 was $174 billion. In 2009, $16.9 billion was spent on drugs for diabetes. The global sales of diabetes pharmaceuticals totaled $35 billion in 2010, and these are expected to rise to $48 billion by 2015. Despite such considerable expenditures, in 2000 only 36% of patients with type 2 diabetes in the United States achieved glycemic control, defined as hemoglobin A1c <7%.

Objective: To review some of the most important drug classes currently in development for the treatment of type 2 diabetes.

Discussion: Despite the 13 classes of antidiabetes medications currently approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes, the majority of patients with this chronic disease do not achieve appropriate glycemic control with these medications. Many new drug classes currently in development for type 2 diabetes appear promising in early stages of development, and some of them represent novel approaches to treatment, with new mechanisms of action and a low potential for hypoglycemia. Among these promising pharmacotherapies are agents that target the kidney, liver, and pancreas as a significant focus of treatment in type 2 diabetes. These investigational agents may potentially offer new approaches to controlling glucose levels and improve outcomes in patients with diabetes. This article focuses on several new classes, including the sodium-glucose cotransporter-2 inhibitors (which are furthest along in development); 11beta-hydroxysteroid dehydrogenase (some of which are now in phase 2 trials); glycogen phosphorylase inhibitors; glucokinase activators; G protein-coupled receptor 119 agonists; protein tyrosine phosphatase 1B inhibitors; and glucagon-receptor antagonists.

Conclusion: Despite the abundance of FDA-approved therapeutic options for type 2 diabetes, the majority of American patients with diabetes are not achieving appropriate glycemic control. The development of new options with new mechanisms of action may potentially help improve outcomes and reduce the clinical and cost burden of this condition.