Diseases

Type 2 Diabetes

The incidence of type 2 diabetes is growing at an alarming rate and has reached epidemic proportions in developed countries around the world. According to the World Health Organization, at least 180 million people worldwide have diabetes and that number will more than double over the next two decades. In the U.S., the total prevalence of diabetes in 2005 was estimated to be 20.8 million people, or 7% of the population.

Type 2 diabetes accounts for 90% to 95% of all diagnosed cases of diabetes. The disease is frequently undiagnosed until complications appear, and approximately one-third of all people with diabetes are undiagnosed.

Type 2 diabetes is a complicated metabolic disorder that involves multiple factors including loss of sensitivity to the effects of insulin, a decrease in the body's ability to produce insulin and the overproduction of glucose by the liver. Uncontrolled diabetes results in abnormally high blood sugar levels, a condition known as hyperglycemia. The long-term adverse effects of hyperglycemia include blindness and loss of kidney function as well as nerve damage, loss of sensation and poor circulation in the extremities, each of which may eventually necessitate amputation. Diabetes is currently the sixth leading cause of death by disease and is the leading cause of kidney disease and non-traumatic lower limb amputations as well as blindness among young adults.

The primary goal in the treatment of diabetes is to maintain tight glycemic control as measured by HbA1c, a broad measure of glucose control over a three month period. FPG (fasting plasma glucose) and PPG (postprandial glucose) are both measures of current glucose levels. Elevated FPG has been associated with the development of microvascular disease complications, including damage to the retina. Elevated PPG has been associated with the development of macrovascular disease, including cardiovascular disease.

There are six classes of oral agents approved for the treatment of type 2 diabetes that are differentiated by their mechanisms of action and effect on either FPG, PPG or both. There are those that improve insulin sensitivity (metformin and thiazoliadinediones, or TZDs), those that increase insulin secretion (sulfonylureas and glinides) and those that block food absorption into the gut (alpha-glucosidase inhibitors, or AGIs). The newest oral agent on the market (dipeptyl peptidase IV, or a DPP-IV inhibitor) focuses on the action of a glucagon-like peptide-1, or GLP-1, a peptide that, like the glinides, enhances glucose-dependent insulin secretion and exhibits other antihyperglycemic actions.

Diabetic Gastroparesis

Delayed gastric emptying and its associated symptoms, or gastroparesis, is a disorder in which the stomach takes too long to empty its contents.  Diabetes is the most common systemic cause of gastroparesis.  Patients with gastroparesis may experience a range of symptoms that severely impair their quality of life.  The most common of these are early feelings of fullness after beginning a meal, abdominal bloating, nausea, vomiting and abdominal pain.  The National Institute of Health has estimated that up to 900,000 type 1 diabetics and nearly 4 million type 2 diabetics have diabetic gastroparesis.  There are only a few medications currently available to treat gastroparesis and these are generally quite weak and associated with unwanted side effects.  In clinical studies, administration of a ghrelin agonist has been shown to increase gastric emptying and may therefore be a significant therapeutic improvement for patients suffering from type 1 diabetic gastroparesis.

Obesity

Obesity is a major health crisis in the U.S. and has become a worldwide epidemic. Obesity has been characterized as "the number one health threat" facing the nation, and is forecasted to become the leading cause of mortality in the U.S., overtaking smoking-related illnesses, all according to the Center for Disease Control and Prevention, or CDC. According to the World Health Organization, or WHO, there are as many as 1.6 billion people worldwide considered to be overweight, 400 million of whom are estimated to be obese. In the U.S., approximately 134 million adults are overweight, of which 63 million are considered obese and 9 million are considered severely obese. Approximately 300,000 deaths per year in the U.S. are associated with obesity according to the Department of Health and Human Services, or HHS. According to the National Health and Nutrition Examination Survey from 1980 to 2002, the prevalence of obesity in the U.S. doubled to approximately 30% of the adult population with an additional 34% being classified as overweight. HHS and the North American Association for the Study of Obesity consider excessive body weight to be associated with a host of complications, including diabetes, hypertension, high cholesterol, coronary artery disease, cancer, liver and pulmonary disease which are often precipitated or exacerbated by the obese condition.

In 2000, HHS estimated the overall annual economic costs of obesity in the U.S. to be $117 billion. Americans spend an estimated $40 billion per year on diet-related products alone. Despite the size of this unmet medical need, the pharmaceutical market to treat obesity is relatively small because there are few therapies currently available and most are ineffective or poorly tolerated by patients. While some patients are candidates for gastric bypass or reduction surgery, the potential complications, including mortality, and the substantial costs and recovery time make it a realistic option only for those patients characterized as morbidly obese.

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