Current Therapies and Emerging Drugs in the Pipeline for Type 2 Diabetes

Diabetes is a chronic, progressive disease that affects approximately 347 million people worldwide.1 In the United States, 25.8 million Americans have diabetes, and another 79 million US adults aged ≥20 years are considered to have prediabetes.2 Diabetes is the leading cause of kidney failure, nontraumatic lower-limb amputations, and new cases of blindness among adults in the United States. It is a major cause of heart disease and stroke and is the seventh leading cause of death among US adults.2 The total estimated cost for diabetes in the United States in 2007 was $174 billion,2 and between 2007 and 2009, the estimated cost attributable to pharmacologic intervention in the treatment of diabetes increased from $12.5 billion to $16.9 billion.3–5 Global sales for diabetes medications totaled $35 billion in 2010 and could rise to $48 billion by 2015, according to the drug research company IMS Health.6,7 In 2009, $1.1 billion was spent on diabetes research by the National Institutes of Health.8 Despite these staggering costs, currently there are still no proved strategies to prevent this disease or its serious complications. KEY POINTS ▸ Approximately 25.8 million adult Americans have diabetes. In 2007, diabetes cost the United States an estimated $174 billion, and in 2009, $16.9 billion was spent on antidiabetes medications. ▸ Nevertheless, the majority of American patients with diabetes do not achieve glycemic control with the currently available pharmacotherapies. ▸ Several novel and promising medications are currently in development, targeting the kidney, liver, and pancreas in the treatment of type 2 diabetes. ▸ Many of these investigational agents involve new mechanisms of action that offer new therapeutic targets and may help improve glucose control in patients with diabetes. ▸ The new drug classes in development include the sodium-glucose cotransporter-2 inhibitors (which are furthest along in development); the 11beta-hydroxysteroid dehydrogenase; glycogen phosphorylase inhibitors; glucokinase activators; G protein-coupled receptor 119 agonists; protein tyrosine phosphatase 1B inhibitors; glucagon-receptor antagonists. ▸ Several of these new classes are associated with low potential for hypoglycemia, representing a potentially new approach to diabetes drug therapy. ▸ The development of new options with new mechanisms of action may potentially help improve patient outcomes and reduce the clinical and cost burden of this chronic disease. According to the 1999–2000 National Health and Nutrition Examination Survey, only 36% of patients with type 2 diabetes achieve glycemic control—defined as hemoglobin (Hb) A1c <7%—with currently available therapies.9 Lifestyle modification remains the most important and effective way to treat diabetes; however, the majority of patients with type 2 diabetes are unable to maintain such a rigid lifestyle regimen. For most patients with type 2 diabetes, pharmacologic intervention will therefore be needed to maintain glycemic control.2 Tables 1 and ​and22 list the 13 classes of medication currently approved by the US Food and Drug Administration (FDA) for the treatment of type 2 diabetes. Despite this abundance of pharmacotherapies, new medications with different mechanisms of action or new approaches to therapy are needed to improve patient outcomes and reduce the clinical and cost burden of this serious condition. Table 1 FDA-Approved Antidiabetic Agents for the Treatment of Type 2 Diabetes Table 2 Insulin Preparations Indeed, the number of diabetes medications for type 2 diabetes is expected to grow in the next few years, considering the many promising investigational therapeutic options currently in development that may gain FDA approval in the future. This article reviews some of the therapies that are currently being tested and may soon become new options for the treatment of type 2 diabetes (Table 3). Table 3 Drugs in the Pipeline for Type 2 Diabetes