CLINICAL
REVIEW ARTICLE
New and Emerging Drugs and Targets for Type 2 Diabetes: Reviewing the Evidence Brien Rex Miller, DO; Hanh Nguyen, DO; Charles Jia-Haur Hu, DO; Chihyi Lin, DO; Quang T. Nguyen, DO, FACP, FACE, FTOS Stakeholder Perspective, page 462
Am Health Drug Benefits. 2014;7(8):452-463 www.AHDBonline.com Received September 29, 2014 Accepted in final form October 28, 2014
Disclosures are at end of text
BACKGROUND: Diabetes is a deadly and costly disease. The number of adults in the United States with newly diagnosed diabetes has nearly tripled from 1980 to 2011. At the current pace, 1 in 3 US adults will have diabetes in their lifetime. Currently, 14 classes of drugs are available to treat type 2 diabetes mellitus, but only 36% of patients with type 2 diabetes achieve glycemic control with the currently available therapies. Therefore, new treatment options are desperately needed. DISCUSSION: Despite the availability of many pharmacotherapies, in 2011 an estimated 3.1 million (14.9%) patients with type 2 diabetes still reported not taking medications to treat their diabetes. Patient compliance is a major obstacle facing practicing clinicians on a daily basis. New treatment options are desperately needed, but efficacy and tolerability are no longer the only criteria contributing to the success of a drug. Ease of administration, convenient dosing frequency, being weight control friendly, and having a low risk for hypoglycemia are important factors for the survival of a new drug in the US healthcare system. The present review is focused on important new drugs and drug classes in the pipeline, as well as on recently approved drugs, including sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 agents, and new insulin therapies, as well as on the technologic improvements in the delivery and dosing frequency of some of the currently available drugs. CONCLUSIONS: In the United States, diabetes can be expected to continue to wreak significant human and financial tolls. The associated complications will continue to climb if they are not controlled and stopped. New therapies for diabetes are clearly needed that will better address these unmet needs. The common threads among the emerging therapies are their convenience of administration and dosing frequency, which are important to the improvement of patient adherence.
T
ype 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 Dr Miller is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr H. Nguyen is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr Hu is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr Lin is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr Q.T. Nguyen is Medical Director, Las Vegas Endocrinology, Clinical Associate Professor, Clinical Education, AZCOM, Adjunct Associate Professor of Endocrinology, Touro University Nevada.
452
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American Health & Drug Benefits
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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.
www.AHDBonline.com
November 2014
l
Vol 7, No 8
New and Emerging Drugs and Targets for Type 2 Diabetes
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
REVIEW ARTICLE
New and Emerging Drugs and Targets for Type 2 Diabetes: Reviewing the Evidence Brien Rex Miller, DO; Hanh Nguyen, DO; Charles Jia-Haur Hu, DO; Chihyi Lin, DO; Quang T. Nguyen, DO, FACP, FACE, FTOS Stakeholder Perspective, page 462
Am Health Drug Benefits. 2014;7(8):452-463 www.AHDBonline.com Received September 29, 2014 Accepted in final form October 28, 2014
Disclosures are at end of text
BACKGROUND: Diabetes is a deadly and costly disease. The number of adults in the United States with newly diagnosed diabetes has nearly tripled from 1980 to 2011. At the current pace, 1 in 3 US adults will have diabetes in their lifetime. Currently, 14 classes of drugs are available to treat type 2 diabetes mellitus, but only 36% of patients with type 2 diabetes achieve glycemic control with the currently available therapies. Therefore, new treatment options are desperately needed. DISCUSSION: Despite the availability of many pharmacotherapies, in 2011 an estimated 3.1 million (14.9%) patients with type 2 diabetes still reported not taking medications to treat their diabetes. Patient compliance is a major obstacle facing practicing clinicians on a daily basis. New treatment options are desperately needed, but efficacy and tolerability are no longer the only criteria contributing to the success of a drug. Ease of administration, convenient dosing frequency, being weight control friendly, and having a low risk for hypoglycemia are important factors for the survival of a new drug in the US healthcare system. The present review is focused on important new drugs and drug classes in the pipeline, as well as on recently approved drugs, including sodium glucose cotransporter-2 inhibitors, glucagon-like peptide-1 agents, and new insulin therapies, as well as on the technologic improvements in the delivery and dosing frequency of some of the currently available drugs. CONCLUSIONS: In the United States, diabetes can be expected to continue to wreak significant human and financial tolls. The associated complications will continue to climb if they are not controlled and stopped. New therapies for diabetes are clearly needed that will better address these unmet needs. The common threads among the emerging therapies are their convenience of administration and dosing frequency, which are important to the improvement of patient adherence.
T
ype 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 Dr Miller is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr H. Nguyen is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr Hu is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr Lin is Resident, Department of Internal Medicine, Valley Hospital Medical Center, Las Vegas, NV; Dr Q.T. Nguyen is Medical Director, Las Vegas Endocrinology, Clinical Associate Professor, Clinical Education, AZCOM, Adjunct Associate Professor of Endocrinology, Touro University Nevada.
452
l
American Health & Drug Benefits
l
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.
www.AHDBonline.com
November 2014
l
Vol 7, No 8
New and Emerging Drugs and Targets for Type 2 Diabetes
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
