This TriMark Publications report describes the specific market segment of the pharmaceutical market for diabetes and two of its related diseases, metabolic syndrome and cardiovascular disease. It begins with a textbook explanation of the biology underlying diabetes, and then it reviews and evaluates widely accepted pharmaceutical approaches to diabetes that are currently in use. Finally, market forecasts and an analysis of products in the worldwide prescriptions market will help the reader understand the significance of past developments and speculate on future possibilities about the market of diabetes therapies as an area of research and investment. The principal objectives of this report are to: 1) identify viable technology drivers through a comprehensive look at various platform technologies for diabetes, metabolic syndrome and cardiovascular disease; 2) provide a complete understanding of the leading diabetes tests that are used for disease prediction, screening, prognosis and monitoring, encompassing their basic principles and applications; 3) discover feasible market opportunities via an identification of high-growth applications in different therapeutic areas, with a focus on the largest and most rapidly expanding markets for diabetes, metabolic syndrome and cardiovascular disease; 4) focus on global industry development through an in-depth analysis of the major world markets for molecular diagnostics, including forecasts for growth; and 5) summarize the blood glucose testing market, including definitions, processes and trends. Market figures regarding the current value of the diabetes drug market are taken from the most recently available data of the global pharmaceutical industry. The following categories of diabetes drugs will be covered herein: 1) rapid-acting insulin; 2) short-activity insulin; 3) intermediate-acting insulin; 4) long-acting insulin; 5) ultra-long-acting insulin; 6) insulin mixtures; 7) sulfonylureas; 8) meglitinides; 9) biguanides; 10) thiazolidinediones; and 11) alpha-glucosidase inhibitors.
TABLE OF CONTENTS
1. Overview 6
1.1 Statement of Report 6
1.2 About this Report 6
1.3 Scope of the Report 7
1.4 Methodology 8
1.5 Executive Summary 8
2. Introduction 12
2.1 Demographics of Diabetes 12
2.1.1 Worldwide Diabetes 12
2.1.2 U.S. Diabetes 12
2.2 Economics of Diabetes 22
3. Understanding the Metabolic Conditions Underlying and Associated with Diabetes 28
3.1 Pre-Diabetes Syndrome 28
3.2 Metabolic Syndrome 29
3.3 Diabetes and Inflammation 30
3.4 Progression of Diabetes 30
3.5 Complications and Co-Morbidities in Type 2 Diabetes 30
3.6 Hypoglycemia and Treatment 33
3.7 Risk Factors and Diabetes 33
3.8 Cardiovascular Disease Facts 35
4. Current Treatment Paradigms 41
4.1 The Worldwide Pharmaceutical Industry 41
4.1.1 Total Diabetes Drug Market Size and Growth 47
4.1.2 Sales of Anti-diabetic Drugs Continue to Rise 50
4.1.3 Epidemiology/Cost of Treatment 53
4.2 Diabetic Medications Overview 53
4.2.1 Recent Trends in Diabetic Drug Usage 55
4.2.2 Factors that are Likely to Influence the Market 56
4.2.3 Anti-Diabetic Drug Therapy Overview 57
4.2.3.1 Sulfonylureas 60
4.2.3.2 Meglitinides 61
4.2.3.3 Biguanides 62
4.2.3.4 Thiazolidinediones (TZDs) 63
4.2.3.5 a-Glucosidase Inhibitors 64
4.2.3.6 Combination Therapy 65
4.2.3.7 Drivers and Trends 65
4.2.3.8 Market Share of Anti-Diabetic Drugs 66
4.2.4 Forecasts for Anti-Diabetic Drugs 67
4.2.4.1 Sales Forecast for the Global Diabetes Market 67
4.2.4.2 The Future 68
4.2.4.2.1 Practice Patterns 69
4.2.4.2.2 New Products in Pipeline 69
4.2.5 Anti-Diabetic Drug Patent Expiry 70
4.2.6 Regulatory Issues 70
4.3 Sulfonylureas and Meglitinides 70
4.3.1 First-generation Sulfonylurea Agents 72
4.3.2 Second-generation Sulfonylurea Agents 73
4.4.1 Thiazolidinediones 73
4.4.2 PPAR Agonists 74
4.5 a-Glucosidase Inhibitors 74
4.6 Insulin Markets 74
4.6.1 Major Players and Market Share 75
4.6.2 Rapid-Acting Insulin 78
4.6.3 Intermediate-Acting Insulin 80
4.6.4 Long-Acting Insulin 80
4.6.5 Ultra Long-Acting Insulin 81
4.6.6 Insulin Mixtures 81
4.6.7 Newly Approved Insulin 82
4.6.8 Pipeline Insulin 83
4.6.9 Insulin in Development 83
4.6.9.1 Inhaled Insulin Overview 84
4.6.9.2 Inhaled Insulin Pipeline 84
4.6.9.3 Oral insulin 85
4.6.9.4 Barriers for Non-Injected Insulin 86
4.6.9.5 Patient Potential for Non-Injected Insulin 86
4.7 Other Anti-diabetic Therapy Drug Candidates 86
4.7.1 Lipid Abnormalities 86
4.7.2 High Blood Pressure 87
4.7.3 Anticoagulants 89
4.8 Biguanides 89
4.9 Drugs Used "Off-Labelé 89
4.9.1 Glucagon-Like Insulinotropic Peptide (GLP-1) 89
4.9.2 Pramlintide (Symlin) 89
4.9.3 Niacin Derivatives 89
4.9.4 Benfluorex 90
4.9.5 D-Chiro-Inositol 90
4.9.6 Exendin-4 90
4.10 Investigational New Agents 90
4.11 New Medicines in Development 90
5. Emerging Oral Anti-diabetes Products 95
5.1 Novel Oral Medications 95
5.2 PPAR agonists 95
5.3 Insulin Mimetics 95
5.4 GLP-1 95
5.5 Immune Modulators 96
5.6 Artificial Pancreas 96
5.6.1 Pancreatic Transplantation 97
5.6.1.1 Pancreatic Organ Transplantation 97
5.6.1.2 Allo-Islet Transplantation 97
5.6.1.3 Transplantation of Encapsulated Pancreatic Cells 97
5.6.1.4 Implantation of Genetically Engineered b-Cells or Embryonic Stem Cells 98
5.6.2 Current Status 98
5.7 Other Type Drugs 99
5.8 New Pipeline Diabetic Drug Candidates 99
5.9 Drug Research Overview 103
6. Projections for the Anti-diabetes Drug Market 106
6.1 Implantable Insulin Pumps 109
6.1.1 Market Share 110
6.1.2 Drivers of Demand for Pumps 114
6.2 Insulin Pills 114
6.3 Transdermal Insulin 115
6.4 Oral Spray Insulin 115
6.5 Inhaled Insulin 116
6.5.1 Important Players 117
6.6 Insulin-Producing Cells 118
6.7 Transplantation Procedures 119
6.8 Anti-Obesity Drug Xenical to Prevent or Delay Development of Type 2 Diabetes 120
7. Diagnosing Diabetes Using In Vitro Laboratory Tests 121
7.1 New Diagnostic Guidelines 121
7.2 Diabetes Tests 121
7.2.1 Fasting Plasma Glucose (FPG) Test 121
7.2.2 Glucose Tolerance Test 122
7.2.3 Test for Glycosylated Hemoglobin 122
7.2.4 Fructosamine 122
7.3 Glucose Monitoring 123
7.3.1 Overview of Market Segment 126
7.3.2 Competitive Strategies 126
7.3.3 Analyses of the Current Market Conditions, Competition and Product Mix 127
7.3.3.1 First-Generation Monitors 127
7.3.3.2 Second-Generation Monitors 128
7.3.3.3 Third-Generation SMBG Technologies 129
7.3.3.4 Product Overview 129
7.3.3.4.1 LifeScan 130
7.3.3.4.2 Roche Diagnostics 133
7.3.3.3 Bayer Diagnostics (Ames Division) 133
7.3.3.3.1 Abbott Diagnostics 135
7.3.3.3.2 Other Players 135
7.3.4 Adjacent Markets 138
7.3.5 What Are the Advantages of Using a Continuous Glucose-Monitoring Device? 138
8. Insulin Delivery Technologies 139
8.1 Lancets and Lancing Devices 139
8.2 Insulin Pens 141
8.3 Injections Aids 145
8.3.1 Automatic Injectors 145
8.3.2 Syringe Magnifiers 145
8.3.3 Insulin Infusers 145
8.4 Insulin Jet Injectors 146
8.5 External Insulin Pumps 146
8.6 Implantable Insulin Pumps 146
8.7 Artificial Pancreas 146
8.8 Insulin Patches 146
8.9 Market Forecasts for Insulin Administration Technologies 147
8.9.1 Insulin Inhalers 147
8.9.2 Mouth Sprays 147
8.9.3 Pills 147
8.9.4 The Patch 148
9. Market Trends, Challenges and Strategic Options 149
9.1 Overview 149
9.2 Diabetes Drug Market Trends 149
9.2.1 Overview 149
9.2.2 Emergence of Therapeutics with Improved Administration Characteristics 149
9.2.3 Increasing Prevalence of Obesity 149
9.3 Diabetes Mellitus Market Challenges 151
9.3.1 Overview 151
9.3.2 Diabetic Pain Therapeutics 151
9.3.3 Market Prospects of Inhalable Drugs and Their Ability to Establish Safety Levels 151
9.3.4 Changing Consumer Preference Drives Product Development in Invasive Technology Segment 152
9.3.5 Non-Invasive Technology for Revenue Potential 152
9.3.6 Developing Countries Emerging as Key Markets for Diabetes Monitoring Devices 152
9.3.7 Consumer-Driven Marketing Campaigns--Essential, though Expensive 153
9.3.8 Escalating Expenditure for R&D and Marketing Triggers Consolidation 153
9.3.9 Market Size Predictions 153
9.3.10 Major Competitors 153
9.4 Strategic Options 154
9.4.1 Overview 154
9.4.2 Combined Self-Testing Glucose Monitor with Insulin Delivery 154
9.4.3 Diabetes Drugs in Pipeline 155
9.5 FDA Therapeutic Targets 158
Appendix 1 159
Appendix 2 160
INDEX OF FIGURES
Figure 1: Demographic Changes in Diabetes Populations in 2010, 2025, 2050 13
Figure 2: Annual Number of New Cases of Diagnosed Diabetes Among Adults Aged 18 to 79 Years, U.S., 1997-2002 14
Figure 3: Crude and Age-Adjusted Incidence of Diagnosed Diabetes per 1000 Population Aged 18 to 79 Years, U.S., 1997-2002 14
Figure 4: Incidence of Diagnosed Diabetes per 1000 Population Aged 18 to 79 Years, by Age, U.S., 1997-2002 15
Figure 5: Age-Adjusted Incidence of Diagnosed Diabetes per 1000 Population Aged 18 to 79 Years, by Sex, U.S., 1997-2002 15
Figure 6: Incidence of Diagnosed Diabetes per 1000 Population Aged 18 to 79 Years, by Sex and Age, U.S., 1997-2002 16
Figure 7: Age-Adjusted Incidence of Diagnosed Diabetes per 1000 Population Aged 18 to 79 Years, by Race, U.S., 1997-2002 16
Figure 8: Distribution of Duration of Diabetes Among Adults Aged 18 to 79 Years, U.S., 2002 17
Figure 9: Number of Hospital Discharges with Diabetes as First-Listed Diagnosis, U.S., 1980-2001 17
Figure 10: Crude and Age-Standardized Hospital Discharge Rates for Diabetes as First-Listed Diagnosis per 1,000 Persons in Diabetic Population, U.S., 1980-2001 18
Figure 11: Distribution of Age at Diagnosis of Diabetes Adults Aged 18 to 79 Years, U.S., 2002 18
Figure 12: Number of Adults with Diabetes Using Diabetes Medication by Type of Medication, U.S., 1997-2002 19
Figure 13: Age-Adjusted Percentage of Adults with Diabetes Using Diabetes Medication by Type of Medication, U.S., 1997-2002 19
Figure 14: Crude and Age-Adjusted Percentage of Adults with Diabetes Using Diabetes Medication, U.S., 1997-2002 20
Figure 15: Percentage of Adults with Diabetes Using Diabetes Medication, by Age, U.S., 1997-2002 21
Figure 16: How Diabetes Dollars Are Spent in the U.S. 25
Figure 17: Standardized Prevalence of Diagnosed and Undiagnosed Diabetes and Impaired Fasting Glucose in the U.S. Adult Population 29
Figure 18: Overlap Between Individuals Diagnosed as Diabetic According to Fasting Plasma Glucose Concentration (ADA criteria) or the Two Hour Glucose Value (WHO Criteria) 34
Figure 19: Sales Forecast for the Global Diabetes Market 68
Figure 20: Utilization: Compliance by Class 77
Figure 21: Analysis of Diabetes Pipeline by Company, 2000 93
Figure 22: Relative Risk of Diabetes Complications by Mean HbA1c 110
Figure 23: Worldwide Diabetes Market, 2000, 2001, 2002 and 2007 111
INDEX OF TABLES
Table 1: Total of People with Diabetes in the World and in Selected Nations, 2000 and 2030 12
Table 2: Age-Adjusted Percentage of Adults with Diabetes Using Diabetes Medication by Type of Medication U.S., 1997-2002 20
Table 3: Crude and Age-Adjusted Percentage of Adults with Diabetes Using Diabetes Medication, U.S., 1997-2002 21
Table 4: Percentages of Adults with Diabetes Using Diabetes Medication by Age, U.S., 1997-2002 22
Table 5: Annual Estimated Cost of Diabetes Care, U.S. 22
Table 6: Impacts of Diabetes on Americans 23
Table 7: Leading Ten Diagnoses by Total U.S. Patient Visits, 2001 23
Table 8: U.S. Incidence of Diabetes by Age, 2005 23
Table 9: Prevalence, Cost and Medicines for Major Diseases in the U.S., 2005 24
Table 10: Top Ten Causes of Death in the U.S., 2003 24
Table 11: Per-Event Costs of Diabetes Complications (Estimated) 26
Table 12: Percentage of Persons with Type 1 Diabetes Experiencing Various Complications 31
Table 13: Novel Risk Factors and Possible Mechanisms of the Excess Risk of Coronary Heart Disease In Type 2 Diabetes Mellitus 32
Table 14: Average Years Gained Free of Diabetes-Related Disease with Intensive Management 33
Table 15: Worldwide Market for Cardiac Care Therapeutics 37
Table 16: Major Causes of End Stage Renal Disease 40
Table 17: Worldwide Clinical Development Costs for Drugs, 2003 41
Table 18: Pharmaceutical R&D Expenditures by World Region, 1990-2003 42
Table 19: U.S. Listed Pharmaceutical Companies Ranked by 2001 R&D Expenditures 42
Table 20: Global Pharmaceutical Sales 43
Table 21: World Pharmaceutical Sales Share by Region 2003 43
Table 22: The Worlds Top-Selling Drugs 2003 44
Table 23: Pharmaceutical Product Sales by Country Market 44
Table 24: Top Pharmaceutical Companies by Market Capitalization 45
Table 25: Leading Therapy Classes Global Pharmaceutical Sales 2000 and 2003 45
Table 26: Leading Ten Therapeutic Classes by U.S. Sales, 2002 46
Table 27: Top Ten Drug Classes by Retail Dollars 46
Table 28: Top Ten Drugs by Retail Dollars 46
Table 29: Top Ten Pharmaceutical Firms by Retail Dollars 47
Table 30: Worldwide Anti-Diabetes Drug Market 48
Table 31: Oral Anti-Diabetic Therapy Major World Markets, 2003 48
Table 32: Worldwide Market Share of Anti-Diabetic Drugs by Type, 2003 and 2007 49
Table 33: The Leading Five Oral Anti-diabetics For 2004 50
Table 34: Oral Hypoglycemic Drugs Used to Treat Type 2 Diabetes 51
Table 35: Worldwide Sales of Avandia 51
Table 36: Worldwide Sales of Actos 52
Table 37: Worldwide Sales of Glucophage 52
Table 38: Worldwide Sales of Starlix 53
Table 39: World Diabetes Pharmaceutical Market 54
Table 40: Trends In Prescription Drug Use Among Patients with Type 2 Diabetes, 1997-2002 56
Table 41: Classes of Oral Hypoglycemic Agents 58
Table 42: Clinical Efficacy of Oral Hypoglycemic Agents 58
Table 43: Average Dose and Cost Comparison of Hypoglycemic Agents 59
Table 44: Average Dose and Cost Comparison of Hypoglycemic Agents 60
Table 45: Relative Efficacy of Oral Agents for Diabetes 60
Table 46: Thiazolidinediones Available for Type 2 Diabetes Mellitus 63
Table 47: Therapeutic Comparison of the Available Thiazolidinediones 63
Table 48: Oralin Sales Forecast Through 2008 66
Table 49: AERx Sales Forecast Through 2008 66
Table 50: HIM 2 Sales Forecast Through 2008 66
Table 51: Oral Anti-diabetic Agents and Their Approved Indications and Uses 72
Table 52: Brand and Generic Names for the Sulfonylureas Sold in the U.S. 72
Table 53: Preparations of Sulfonylurea Tablets 73
Table 54: Worldwide Insulin Sales 75
Table 55: Worldwide Insulin Sales and Market Share by World Region 2003 75
Table 56: Worldwide Insulin Sales and Market Share by Company, 2003 76
Table 57: U.S. Insulin Sales and Market Share by Company, 2003 76
Table 58: U.S. Insulin Sales, 2000-2009 76
Table 59: Worldwide Recombinant Human Insulin Sales and Market Share by Company, 2005 78
Table 60: Pharmacokinetics of Available Insulins 78
Table 61: Action Times for Each Insulin 81
Table 62: Key Drivers of the Type 2 Diabetes Insulin Market to 2012 86
Table 63: Lipoprotein Risk Levels and Treatment Goals in Adult Patients with Diabetes 87
Table 64: Agents for Lowering Lipid Levels in Patients with Dyslipidemia 87
Table 65: Suggested Pharmacological Treatment Agents for Hypertension in Patients with Diabetes 88
Table 66: New Drugs in Human Clinical Trials by Disease Type 94
Table 67: GLP-1 Pipeline: Selected Drugs in Development that Target GLP-1 96
Table 68: Cells of the Pancreas 98
Table 69: Selected Mid-2004 Press Releases on Emerging Anti-diabetes Agents 99
Table 70: Diabetes Agents in the Pipeline 100
Table 71: Control Averages by Treatment 110
Table 72: Reduced Risk for Various Diseases When Blood Glucose is Near Normal 110
Table 73: Worldwide Diabetes Market, through 2007 ($ Millions) 111
Table 74: Types of Insulin Pumps on the Market 111
Table 75: Laboratory Assessment of Diabetic Vascular Disease 123
Table 76: The Global Population of Persons with Diabetes 124
Table 77: The Glucose Market for OTC Testing in the U.S., 1996-2007 125
Table 78: The Glucose Market for OTC Testing Worldwide, 2000-2007 125
Table 79: OTC Glucose Meter U.S. Market Share for Blood Glucose Measurements 126
Table 80: Lancet Characteristics 141
Table 81: Lancing Device Characteristics 141
Table 82: Worldwide Insulin Injector Pen Dollar Volume, 1998-2006 143
Table 83: Insulin Delivery Systems Percent Retail Market Share 144
Table 84: Insulin Delivery Systems Percent Retail Market Share by Company, 2003 145
Table 85: Summary of Inhaled Insulin Products 148
Table 86: Worldwide Diabetes Drugs in Pipeline, 2004 155
Table 87: Top Therapeutic Drug Categories Worldwide, 2004 156
Table 88: Top Therapeutic Categories in U.S. Development, 2003 156
Table 89: Pharmaceutical Companies Number of Products in Development 156
Table 90: Pharmaceutical Companies Number of Diabetes Products in Development 157
Table 91: Drugs in Preclinical Testing, 2004 157
Table 92: New Diabetes Drugs in Pipeline without Major Pharma Alliances 158a
