Chapter 1: Introduction
1.1. Metabolic Syndrome: A Multifaceted Syndrome by Many Names
1.2. Etiology of Primary Components: The Vicious Cycle of “Diabesity”
1.3. Further Sequels: Endothelial Dysfunction, Inflammation, and Psychiatric Implications
1.4. The National Institutes of Health ATP III Guidelines and Definition
Chapter 2: Epidemiological Aspects
2.1. Overweight/Obesity and Lack of Physical Activity
2.2. Insulin Resistance and Diabetes
2.3. Elevated Blood Pressure and Hypertension
2.4. Dyslipidemia
2.5. Estimates for Prevalence and Incidence of the Metabolic Syndrome
Chapter 3: Current Options for Pharmacological Intervention
3.1. Limited Potential for Lifestyle Modifications
3.2. Current Pharmacological Treatment of Component Entities
Drugs for Insulin Resistance and Emerging Type 2 Diabetes
-Sulphonylureas—Stimulators of Basal Insulin Release
-Post-Prandial Insulin Secretion Stimulators—the “Meglitinides”
-Insulin Sensitizers
--Metformin (Bristol-Myers Squibb’s glucophage/glucamet; generics)
-Glitazones—The Original PPAR Agonists
--Avandia (rosiglitazone maleate, GlaxoSmithKline)
--Actos (pioglitazone HCl, Eli Lilly and Takeda)
-Glitazone/Metformin Fixed Combination Products
-Alpha-Glucosidase Inhibitors: Intestinally Acting Glucose Retardants
Drugs for Dyslipidemia: Fibrates, Statins, and Niacin
-Fibrates
--Lopid (Pfizer’s gemfibrozil and generics)
--TriCor/Lipanthyl/Lipidil (fenofibrate, Abbott Laboratories and Groupe Fournier; generics)
--Bezalip (Roche’s bezafibrate)
--Lipanor/Modalim (Sanofi-Aventis’ ciprofibrate)
-Statins
-Cholesterol Absorption Inhibitors
--Ezetimibe (Schering-Plough/Merck & Co.’s Zetia)
-Niaspan and Advicor
Hypertension: Drug Class Differences in the Metabolic Effects
Weight Reduction Agents
-Xenical (orlistat, Roche)
-Meridia/Reductil (sibutramine, Abbott Laboratories)
-“Short-Term Slimmers”: No Relevance to the Metabolic Syndrome
Chapter 4: Unmet Treatment Need in the Metabolic Syndrome
4.1. Unmet Need in Current Drugs and Treatment Schedules
Weight Reduction Drugs
Glucose-Lowering Drugs
Lipid-Lowering Drugs
Anti-Hypertensive Drugs
4.2. Genetic Predisposition and Tailored Therapies: A Great Task Ahead
4.3. Unconventional Approaches: A Role for Neurotrophic Factors?
4.4. Summary
4.5. SWOT Exhibits for the Metabolic Syndrome Component-Disorder Drugs
Chapter 5: Improvements Ahead—Breakthroughs on the Horizon?
5.1. Pharmacological Strategies to Support Weight Loss: A Bumpy Road
Regeneron’s Axokine: A Nerve Growth Factor Agonist Completing Clinical Development
Acomplia (rimonabant) and Other CB1 Receptor Antagonists for Slimming
New Pancreatic Lipase Inhibitors in the Pipeline
Symlin (Pramlintide acetate, an Analog of Amylin)
An Appetite Suppressant from a South African Cactus
Targeting the Adrenergic System—Adjusting the Metabolic Rate
5-HT2c Receptor Agonists
Neuropeptide Y Receptor Agonists
Melanocortin Receptor Agonists
5.2. Potential Treatments for Insulin Resistance and Diabetes
Dual PPAR Stimulators—A New Class of Drugs Tailored to Metabolic Syndrome Therapy
Dipeptidyl Peptidase Inhibitors—Blocking Degradation of Glucagon- Like Peptide 1
Glucagon-Like Peptide Analogs
Sodium-Dependent Glucose Co-Transporter (SGLT) Inhibitors
An Antisense PTP-1B Gene Silencer
5.3. New Developments in Lipid Disorders
Cholesteryl Ester Transfer Protein (CETP) Inhibitors
Ibrolipim: A Lipoprotein Lipase Activator
An Antibody Mix for Dyslipidemia
Inhibition of Acetyl-CoA Carboxylase
Antisense Drugs
Omacor, an FDA-Approved Nutritional Supplement
5.4. Targeting Hypertension in the Metabolic Syndrome
Renin Inhibitors
Selective Aldosterone Blockade
Endothelin A Receptor Antagonists
5.5. Potential Improvements in the Therapy of Gout
Chapter 6: U.S. Market Forecast for Metabolic Syndrome Component Disorders: 2003-2018
6.1. Introduction
6.2. Methodology and Sources
6.3. United States Market Forecast for Dyslipidemia
Market Overview
Patent Expirations
Drug Launches
Epidemiology
6.4. United States Market Forecast for Type 2 Diabetes
Market Overview
Patent Expirations
Drug Launches
Epidemiology
6.5. United States Market Forecast for Obesity
Market Overview
Patent Expirations
Drug Launches
Epidemiology
6.6. United States Market Forecast for Hypertension
Market Overview
Patent Expirations
Drug Launches
Epidemiology
Chapter 7: Pipeline and Research Program Profiles
7.1. Sanofi-Aventis
7.2. Eli Lilly
7.3. Novo Nordisk A/S
7.4. Bristol-Myers Squibb
7.5. GlaxoSmithKline
7.6. Roche Group
7.7. Merck & Co.
7.8. DeveloGen AG
7.9. Wellstat Therapeutics Corp.
7.10. Amylin Pharmaceuticals
7.11. Ligand Pharmaceuticals
7.12. Regeneron Pharmaceuticals, Inc.
7.13. Biovitrum AB
7.14. Summary
References
Glossary
Index
