New and emerging drugs and targets for type 2 diabetes: reviewing the evidence.

Type 2 diabetes mellitus is an ongoing medical problem that clinicians deal with on a daily basis. The necessity of treating diabetes adequately is essential because of the many comorbidities and complications associated with uncontrolled diabetes. These comorbidities are very costly to the healthcare system and to the patient. In 2012, 28.9 million adult patients in the United States were diagnosed or undiagnosed with diabetes; of these, 15.5 million were men and 11.2 million were aged ≥65 years.1 The number of newly diagnosed patients with diabetes in 2012 was approximately 1.7 million, the majority of whom were aged 45 to 64 years.1 The prevalence of diabetes is still increasing. The number of US adults (aged 18–79 years) with newly diagnosed diabetes has nearly tripled in the past few decades, from 493,000 in 1980 to more than 1.5 million in 2011.2 At the current pace, approximately 1 in 3 US adults will have diabetes in their lifetime.1 The numerous comorbidities associated with diabetes include, but are not limited to, kidney failure, obesity, coronary artery disease, peripheral vascular disease, hypertension, stroke, and amputations.1 In the years 2003–2006, cardiovascular (CV) disease mortality rates were approximately 1.7 times higher among adults aged ≥18 years with diagnosed diabetes than among adults without diagnosed diabetes.1 In 2010, after adjusting for population age differences, hospitalization rates for heart attack and stroke were 1.8 times and 1.5 times higher, respectively, among adults aged ≥20 years with diagnosed diabetes than among adults without diagnosed diabetes.1 The estimated total cost for type 2 diabetes mellitus was $245 billion in 2012, of which $176 billion was in direct medical expenditures.1 With these trends, the cost and debilitating effects of this disease are only going to escalate, unless better glycemic control is achieved. The older medications for diabetes, especially insulin and sulfonylureas, are associated with the common side effects of weight gain and hypoglycemia, which can be costly to the healthcare system. A retrospective study evaluated the incidence and cost of hypoglycemic events in patients with type 2 diabetes during 4 years.3 The analysis showed that the mean cost per 1 inpatient admission was $17,564, including $1387 for an emergency department visit and $394 for an outpatient visit. The total direct medical cost of hypoglycemia during the 4-year study was $52,223,675, which accounted for approximately 1% of all the inpatient costs, 2.7% of emergency department costs, and 0.3% of outpatient costs.3 The annual medical cost of obesity is currently estimated to be approximately $147 billion.4 Using drugs for the treatment of diabetes that can aid in weight loss rather than increase weight gain is cost-effective and can aid in patient adherence. In one study, researchers estimated that 1% of weight loss in 1 year could decrease a patient's total healthcare cost by approximately $213 per patient who is using antidiabetic medications.5 Another study ascertained that patients with type 2 diabetes mellitus who lost weight with a treatment regimen are more likely to adhere to their regimen than patients who gain weight with their medication.6 Increased adherence to oral antihyperglycemic agents has been shown to be associated with reduced healthcare utilization as well as cost.7 As many as 14 classes of drugs are currently available for the treatment of type 2 diabetes mellitus.8 Despite the availability of pharmacotherapies, an estimated 3.1 million (14.9%) US adults with type 2 diabetes were still not taking a medication for diabetes in 2011.9 According to the 1999–2000 National Health and Nutrition Examination Survey, only approximately 36% of patients with type 2 diabetes achieve glycemic control—defined as a hemoglobin (Hb)A1c level of <7%—with the currently available therapies.10 New medications with different mechanisms of action or with novel approaches to therapy are needed to improve patient outcomes and to reduce the clinical burden of this condition. The current article reviews some of the newly approved therapies by the US Food and Drug Administration (FDA), as well as those that are currently being tested as new options for the treatment of type 2 diabetes mellitus. Most drugs in this review have voucher and coupon programs provided by the manufacturer to offset the cost of the medications (Table). Table Table Emerging Therapies for the Treatment of Patients with Diabetes: Monthly Costs The risks and benefits of each drug discussed in this article should be weighed appropriately when a drug regimen is chosen for a particular patient with diabetes. In addition, because many of these drugs have only recently become available in the United States, long-term evidence from real-world utilization is lacking. Furthermore, the FDA has requested postmarketing studies for some of these new agents, to investigate the potential risks for patients with diabetes to ensure that these new classes of drugs are safe for long-term use in this patient population. KEY POINTS ▸ The number of US adults with newly diagnosed diabetes has nearly tripled from 1980 to 2011 and continues to rise. ▸ Despite the many drugs available for treating type 2 diabetes, only 36% of patients in the United States achieve glycemic control; patient adherence is a major obstacle. ▸ Efficacy and tolerability are no longer the only criteria for the success of a new drug; ease of administration, convenient dosing frequency, being weight control friendly, and having a low hypoglycemic risk are important factors for new antidiabetes drugs. ▸ New oral drug classes have recently been approved by the FDA and more are in development, most of which are once-daily agents. ▸ All new injections for diabetes are now in a pen format to improve patient adherence. ▸ Significantly, the new agents being introduced to the market are either weight-friendly or can induce weight loss, and have lower risks for hypoglycemia. ▸ At a mean total cost of $17,564 per hypoglycemic episode requiring hospitalization, this can be a meaningful improvement to the healthcare system as a whole.