Introduction

Diabetes mellitus is a chronic metabolic disorder that results due to a failure of the body to produce the hormone insulin and/or an inability of the body to respond adequately to circulating insulin. Type 1 diabetes, previously referred to as insulin-dependent diabetes mellitus (IDDM), occurs most commonly in children or young adults and constitutes 5–10% of the diagnosed diabetes patient population. Type 2 diabetes, previously known as adult-onset diabetes or non-insulin-dependent diabetes mellitus (NIDDM), accounts for 90–95% of diagnosed diabetes cases globally and typically develops in middle-aged adults. The 2008 prevalence of diabetes mellitus, together in the seven major markets, was 8.5% with Germany having the highest prevalence rate at 11.8%. But the disease has been growing at epidemic proportions, a fact that has driven extensive R&D in this therapy area.

The global diabetes market was worth $27.3bn in 2008 and was led by insulin analogs which captured 45.0% of the market followed by glitazones that captured a share of 22.8%. US is the largest diabetes market globally with sales of $12.9b in 2008 and a market share of 47.6%. However the highest growth in sales y-o-y was exhibited by several early emerging economies such as UAE at 59.7%.

Scope of this report

• Epidemiological analysis of the therapy area and forecast prevalence over the period 2009-14 .

• Forecasts and analysis of the key products in the diabetes market over the period 2009-14 spread across the major classes of treatments.

• Overview of key events in the global diabetes market that have impacted treatment trends and sales potential.

• Strategic and growth analysis of leading pharmaceutical corporations based on sales focus by drug class, currently marketed products and R&D product portfolios.


Key findings from this report


• Biguanides, mainly comprised of metformin, are the core first line therapy in diabetes care. These drugs have been used in diabetes therapy for over a decade. Some of their advantages include, efficacy, low cost, extensive experience, lack of incidences of hypoglycemia and weight neutrality. Metformin lost patent protection in 2002 and the class is now much genericized and has been ceding market share to other therapies.

• Insulin captured the largest market share (45%) among available diabetes treatments and is likely to dominate the market in the forecast period. However, though insulin analogs have become well established in the market, inhaled insulin is yet to make its mark.

• Significant R&D has been observed in the pre-insulin market leading to the development of several novel and safer therapies. The comparative performance of these therapies, such as the DPP-IV inhibitors and GLP-1 analogs would shape the diabetes market landscape through 2014 and in the long term.

Key issues

• Revised FDA guidelines make the regulatory environment challenging
In December 2008, the FDA announced that the companies developing diabetes drugs will be required to conduct longer and larger studies to avoid any “unacceptable” cardiovascular risk. Companies are now required to conduct meta analyses for cardiovascular safety in the Phase II and III trials and rule out the possibility of an increased cardiovascular disease risk by 80% or more.

• Inhaled insulin still a distant reality
Insulin therapy takes up the biggest share of diabetes treatment and has been an area of extensive research. While several different purer forms of insulin have emerged over a period of time, nasally administered insulin is still a distant reality. Inhaled insulin may aid compliance, leading to superior long term outcomes. Pfizer/Nektar’s Exubera was the first to be launched inhaled insulin but it had a troubled launch and was subsequently discontinued in October 2007. The only inhaled insulin which is still under development is Technosphere, being developed by Mannkind/Afresa. This insulin uses a technology that facilitates absorption of proteins and peptides through the pulmonary route.

Use this report to:

• Which companies were the leading players in the diabetes therapy area in 2008?

• How have recent major launches from the key market players performed?

• Which companies will become the key players in the diabetes market over the period 2009-14?

• Which products will be impacted by generic competitors over the period 2009-14?

Table of Contents
The Diabetes Market Outlook to 2014
Executive summary 10
Patient potential 10
Global market analysis 10
Pipeline analysis 11
Leading players of the global diabetes market 12
Chapter 1 Scope and methodology 16
Scope 16
Methodology 16
Scope of IMS data 16
Chapter 2 Patient potential 20
Summary 20
Introduction 20
What is diabetes? 20
Types of diabetes 22
Type 1 diabetes 22
Type 2 diabetes 24
Gestational diabetes mellitus 25
Impaired glucose tolerance 26
Diabetic complications 26
Epidemiology 28
Diagnosis 29
How is diabetes measured? 31
Treatment algorithm 32
Chapter 3 Global market analysis 38
Summary 38
Introduction 39
Market analysis by country 39
Licensing trends 43
Key events/trends in the diabetes market 43
FDA’s revised guidelines on longer, larger cardiovascular risk studies for diabetes drugs 43
Newer agents recommended by NICE in diabetes treatment 44
A prophylactic treatment for children at high risk 45
GSK discontinued development of remogliflozin 45
Takeda’s Phase II loss of TAK-379 46
Novo Nordisk’s Prandin lawsuit 46
Market analysis by drug class 47
Diabetes drug classes 47
The insulin landscape 49
Human insulins 52
Animal insulins 61
Drugs targeting underlying causes 61
Glitazones 62
Sulfonylurea 67
Biguanides 69
DPP-IV inhibitors 71
Alpha-glucosidase inhibitors 74
Glinides 76
Glucagon-like peptide-1 agonists 78
DPP-IV and GLP-1 differences 80
Insulin devices 81
Insulin pump therapy 81
Therapy area sales forecast 82
Leading brands of the diabetes market 82
Generic erosion among the leading brands 84
Leading brands sales forecast 85
Chapter 4 Pipeline analysis 88
Summary 88
Introduction 89
Emerging trends/key events in diabetes R&D 89
Emerging therapies in the diabetes market 89
Inhaled insulin still a distant reality 90
Hitherto unexplored avenues in diabetes R&D: magnesium, chromium and vanadium 91
SGLT-2 inhibitors yet to prove their potential 91
Other novel mechanisms under development 92
Profiles of key pipeline products 93
Drugs under registration/recently approved 94
Victoza (liraglutide): Novo Nordisk 94
Onglyza (saxagliptin): BMS/AstraZeneca 97
SYR322 (alogliptin): Takeda 98
Byetta LAR (exenatide long-acting release): Eli Lilly, Amylin,
Alkermes 100
Syncria (albiglutide): GlaxoSmithKline 102
Ondero (linagliptin): Boehringer Ingelheim 103
R1583 (taspoglutide): Roche/Ipsen 105
AVE0010/ZP10: Sanofi-Aventis 106
BMS-512148 (dapagliflozin): AstraZeneca/BMS 108
Teplizumab: Eli Lilly/MacroGenics 110
Competitive dynamics of the investigational drugs 112
Key pipeline compounds sales forecast 114
Chapter 5 Leading players of the global diabetes market 116
Summary 116
Introduction 117
Detailed analysis of the diabetes market players 119
Novo Nordisk 119
Overview 119
Drug class focus 119
Marketed product portfolio 120
R&D pipeline analysis 123
Novo Nordisk: strategic growth analysis 124
Takeda 127
Overview 127
Drug class focus 127
Marketed product portfolio 128
R&D pipeline analysis 129
Takeda: strategic growth analysis 130
Sanofi-Aventis 131
Overview 131
Drug class focus 131
Marketed products portfolio 132
R&D pipeline analysis 135
Sanofi-Aventis: strategic growth analysis 136
Eli Lilly 137
Overview 137
Drug class focus 137
Marketed products portfolio 138
R&D pipeline analysis 140
Eli Lilly: strategic growth analysis 141
Merck & Co. 142
Overview 142
Drug class focus 142
Marketed products portfolio 143
R&D pipeline analysis 145
Merck: Strategic growth analysis 146
Other major players in the diabetes market 147
GSK 147
Boehringer Ingelheim 148
Leading players' outlook through to 2014 149
Chapter 6 Appendix 152
IMS data 152
Glossary 153
Index 154

List of Figures
Figure 2.1: Production of insulin and its action 21
Figure 2.2: Diabetes treatment algorithm 34
Figure 3.3: Global market sizes, 2008 40
Figure 3.4: Global sales of types of diabetes brands ($m), 2008 43
Figure 3.5: Relative positions of different types of insulins in the insulin market, 2008 51
Figure 3.6: Relative positions of different diabetes drug classes, 2008 62
Figure 4.7: Leading late-stage R&D products in the diabetes market, 2009 93
Figure 5.8: Competitive dynamics of the top 10 diabetes players, 2007–08 118
Figure 5.9: Drug class focus of Novo Nordisk, 2008 120
Figure 5.10: Drug class focus of Takeda, 2008 127
Figure 5.11: Drug class focus of Sanofi-Aventis, 2008 132
Figure 5.12: Drug class focus of Eli Lilly, 2008 138
Figure 5.13: Drug class focus of Merck, 2008 143

List of Tables
Table 2.1: Estimated prevalence of diabetes mellitus across the seven major markets, 2008 28
Table 2.2: Forecast prevalence of diabetes mellitus across the seven major markets, 2008–14 29
Table 3.3: USA diabetes drug sales by ATC3 class, 2008 US$ millions 40
Table 3.4: French diabetes drug sales by ATC3 class, 2008 US$ millions 41
Table 3.5: German diabetes drug sales by ATC3 class, 2008 US$ millions 41
Table 3.6: Italian diabetes drug sales by ATC3 class, 2008 US$ millions 41
Table 3.7: Japanese diabetes drug sales by ATC3 class, 2008 US$ millions 42
Table 3.8: Spanish diabetes drug sales by ATC3 class, 2008 US$ millions 42
Table 3.9: UK diabetes drug sales by ATC3 class, 2008 US$ millions 42
Table 3.10: Distribution of the global diabetes market by drug class, 2007–08 49
Table 3.11: Characteristics of different types of insulin 50
Table 3.12: Leading brands in the fast-acting insulin category, 2008 52
Table 3.13: Characteristics of NovoRapid 53
Table 3.14: Characteristics of Humalog 54
Table 3.15: Leading brands in the long-acting insulin category, 2008 55
Table 3.16: Characteristics of Lantus 56
Table 3.17: Leading brands in the intermediate-acting insulin category, 2008 58
Table 3.18: Characteristics of Protaphane HM 59
Table 3.19: Leading brands in the intermediate- and fast-acting insulin category, 2008 59
Table 3.20: Characteristics of NovoMix 60
Table 3.21: Leading brands in the intermediate- and long-acting insulin category, 2008 61
Table 3.22: Leading brands of the glitazones drug class, 2008 63
Table 3.23: Leading brands of the sulfonylureas drug class, 2008 68
Table 3.24: Leading brands of the biguanides drug class, 2008 70
Table 3.25: Leading brands of the DPP-IV drug class, 2008 72
Table 3.26: Strategic growth analysis of Januvia 73
Table 3.27: Leading brands of the AGI drug class, 2008 75
Table 3.28: Leading brands of the glinides drug class, 2008 77
Table 3.29: Leading brands of the GLP-1 agonists drug class, 2008 79
Table 3.30: Major differences between GLP-1 agonists and DPP-IV inhibitors 81
Table 3.31: Diabetes market sales forecast by drug classes ($m), 82
Table 3.32: Leading brands of the global diabetes market, 2008 83
Table 3.33: Generic erosion index of key diabetes brands 84
Table 3.34: Top 10 brands of the diabetes market, sales forecast 2008–14 85
Table 4.35: Select late-stage diabetes R&D pipeline, 2008 94
Table 4.36: An overview of Victoza 95
Table 4.37: An overview of Onglyza 97
Table 4.38: An overview of alogliptin 99
Table 4.39: An overview of Byetta LAR 100
Table 4.40: An overview of Syncria 102
Table 4.41: An overview of Ondero 103
Table 4.42: An overview of taspoglutide 105
Table 4.43: An overview of AVE0010/ZP10 107
Table 4.44: Ongoing Phase III trials of AVE0010/ZP10 108
Table 4.45: An overview of dapagliflozin 109
Table 4.46: Reduction in HbA1c on administering dapagliflozin 110
Table 4.47: An overview of teplizumab 111