Diabetic Nephropathy - Prevalence and Therapeutic Potential
The diabetic microvascular complication, nephropathy, is a condition with high unmet therapeutic needs. It is linked with significant increases in morbidity and mortality risk, and is the most common cause of ESRD in the US and Europe. Despite the efforts to address the increasing incidence of both type 1 and type 2 diabetes, the diabetic population is set to increase by 72% between 2003 and 2025. Access new data from Datamonitor's 380 physician sample survey on the prevalence and progression of diabetic nephropathy in seven major markets. Understand the views of diabetologist and nephrology opinion leaders on the potential for prescribing ACE inhibitors combined with ARBs in diabetes.
Table of Contents
- EXECUTIVE SUMMARY - page 4
- Introduction - page 4
- Scope and coverage of the Brief - page 4
- Key findings about the the topic - page 5
- EPIDEMIOLOGY - page 6
- Definition - page 6
- Etiology of diabetic nephropathy - page 8
- The role of hypertension in diabetic nephropathy - page 8
- Prevalence of nephropathy in type 2 diabetics - page 9
- Progression of diabetic nephropathy in type 2 patients. - page 9
- The growing burden of ESRD on healthcare systems - page 12
- TREATMENT OF DIABETIC NEPHROPATHY - page 14
- Glucose control in diabetic nephropathy - page 14
- Importance of blood pressure control - page 14
- Benefits of ACE inhibition - page 17
- Mechanism of action of ACE inhibitors - page 17
- Data supporting the renoprotective benefits of ACE inhibitors. - page 17
- The AASK study (2001): ramipril vs. metoprolol - page 18
- The MICRO-HOPE study (2000): the benefits of ramipril - page 19
- Renoprotection with ARBs - page 20
- Theoretical advantages of ARB therapy - page 20
- ARBs: a second-line therapy option? - page 21
- Trials with ARBs - page 21
- Avapro (irbesartan) - page 21
- PRIME - page 21
- IDNT - page 21
- IRMA II - page 22
- Discussion - page 22
- Cozaar (losartan) - page 22
- RENAAL - page 22
- Discussion - page 23
- RENAAL - page 22
- Avapro (irbesartan) - page 21
- Further development of the ARB class for diabetic nephropathy - page 25
- ABCD-2V: valsartan in diabetic blood pressure control - page 27
- DETAIL: telmisartan and enalapril against diabetic nephropathy - page 27
- DIRECT: candesartan in diabetic retinopathy - page 28
- PROTECTION program - page 29
- AMADEO/VIVALDI: telmisartan vs losartan/telmisartan vs valsartan - page 29
- TRENDY: telmisartan in endothelial dysfunction - page 29
- ONTARGET: telmisartan in combination with ramipril - page 30
- Comments - page 30
- Potential of the ACE/ARB combination - page 31
- Marketing rationale for the ACE/ARB combination - page 31
- The CALM study (2000): candesartan and lisinopril combination - page 31
- COOPERATE trial (2003): losartan and trandolapril combination - page 32
- Candesartan in combination with lisinopril, enalapril or captopril - page 32
- Marketing rationale for the ACE/ARB combination - page 31
- THE NEED FOR NOVEL AGENTS IN THE TREATMENT OF NEPHROPATHY - page 35
- New compounds should target the underlying disease - page 35
- New approaches for diabetic microvascular complications - page 35
- Inhibitors of aldose reductase (ARI) - page 36
- Protein kinase C-beta inhibitors - page 36
- Advanced glycation endproduct (AGE)-inhibitors - page 37
- Potential treatments for diabetic nephropathy - page 37
- AS-3201 - page 38
- Ruboxistaurin (LY333531) - page 39
- ALT-711 - page 39
- ALT-946 - page 40
- Pyridorin - page 40
- KRX-101 - page 40
- Eplerenone - page 41
- Aliskiren - page 42
- Conclusion - page 42
- APPENDIX - page 43
- Bibliography - page 43
- Epidemiology - page 43
- Treatment and novel agents - page 43
- Disclaimer - page 45
- Bibliography - page 43
- List of Tables
- Table 1: Changes in kidney structure and function in diabetic nephropathy - page 7
- Table 2: Estimated prevalence of type 2 diabetic nephropathy in the seven major markets, 2003 - page 9
- Table 3: Number of type 2 patients affected by diabetic nephropathy and time of progression across the seven major markets (millions), 2003 - page 10
- Table 4: Renal transplantation, hemodialysis and peritoneal dialysis prevalence rates by country (PMP), 2002 - page 12
- Table 5: Hemodialysis population by country (thousands), 2002–12 - page 12
- Table 6: Trends in target blood pressure and therapies to reduce nephropathy risk in patients with diabetes or kidney disease - page 15
- Table 7: Key clinical trials for assessing the renoprotective effect of ARBs - page 26
- Table 8: Overview of nephropathy pipeline, 2003 - page 38
- List of Figures
Figure 1: Estimated progression of diabetic nephropathy in type 2 diabetes across the seven major markets - page 11
- List of Figures
- Figure 2: Increased risk of death and diabetic nephropathy - page 11
- Figure 3: Hemodialysis population by country, 2002–12 - page 13
- Figure 4: Mechanism of action of ACE inhibitors - page 17
- Figure 5: Mechanism of action of ARBs - page 20
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