Diabetes

Inhaling your daily insulin

In a move that has massive implications for diabetics worldwide, the FDA has been advised to approve Exubera, a revolutionary powdered insulin that is administered by oral inhalation. Callan Emery reports.




An estimated 30 million people world-wide had diabetes in 1985. By 1995, this number had shot up to 135 million. In 2000 at least 171 million people worldwide had diabetes. This figure is likely to more than double by 2030 to 366 million, according to the WHO. WHO says that overall, direct healthcare costs of diabetes range from 2.5% to 15% annual healthcare budgets, depending on local diabetes prevalence and the sophistication of the treatment available.

However, it is not only the cost to the health sector that is enormous, the cost to individuals is also immense and includes medical care, drugs, insulin and other supplies such as special dietary supplements. And there are also the intangible costs like pain, anxiety, inconvenience and general lower quality of life which have a great impact on the lives of diabetics.

There is no denying that diabetics have a hard time of it. Beside the strict dietary regimen, many also have to put up with painful daily injections of insulin. But there may be very welcome relief in store which could see diabetics reliant on subcutaneous insulin injections happily discarding their much detested needles.

The US Federal Drug Administration (FDA) Advisory Committee voted (7 to 2) on 8 September that the FDA approve Exubera, a novel, dry powdered, rapid acting insulin administered orally through an inhaler for use in adults with type 1 and type 2 diabetes.

If approved it will forever change the way diabetics administer their daily insulin dose. A “yes” vote usually means FDA approval is only months away as the agency usually follows the advice of its experts.

The FDA, however, is not obliged to follow the recommendations of the advisory committee. Exhubera (insulin [rDNA origin] powder for oral inhalation) is developed by Pfizer, Sanofi-Aventis and Nektar Therapeutics. Pfizer and Sanofi-Aventis have a global agreement to codevelop, co-promote and co-manufacture inhaled insulin.

Nektar is responsible for manufacturing the fine insulin powders and supplying the inhalers. According to the manufacturers Exubera “has proved generally as effective as injected insulin in clinical trials. More than 3,500 patients in clinical trials worldwide have taken Exubera, some for as long as seven years. Results from Phase III clinical trials suggest that Exubera may be as efficacious as injected insulin and superior to oral agents in lowering blood glucose in patients with diabetes.”

The FDA Advisory Committee did, however, raise concerns regarding the limited testing in smokers, people with lung disease and in young children. In response, Declan Doogan, Pfizer's head of development, told Reuters that the company was prepared to conduct a follow-up monitoring programme on Exubera patients.

The panel's vote means a lot to the five competing drug makers with inhalable insulin in the pipeline. Eli Lilly & Co, Alkermesand and Mannkind Corp are developing dry powder insulin products. Also, Novo Nordisk and Aradigm Corp are working on inhalable liquid insulin. These products are at least two years behind Exubera in the development process, a according to a report on CNN Money.

According to the FDA Advisory Committee, Exubera is native-sequence recombinant human insulin in a drug-device combination product for administration via inhalation … for the treatment of diabetes mellitus, both type 1 and type 2. The manufactures say Exubera is a mealtime insulin that is inhaled through the mouth into the lungs prior to eating, using a proprietary inhalation device and powdered insulin formulation.

“Exubera closely mimics the normal physiological insulin response to meals by quickly being absorbed into the bloodstream to reduce meal-related spikes in glucose levels in people with diabetes. However, according to some sources, diabetics will have to inhale about seven times as much insulin as they would inject in order to get the same effect.

Diabetes – the facts

Diabetes mellitus is a chronic disease caused by inherited and/or acquired deficiency in production of insulin by the pancreas, or by the ineffectiveness of the insulin produced. Such a deficiency results in increased concentrations of glucose in the blood, which in turn damage many of the body's systems, in particular the blood vessels and nerves. There are two principle forms of diabetes:

Type 1 diabetes (formerly known as insulindependent) in which the pancreas fails to produce the insulin which is essential for survival. This form develops most frequently in children and adolescents, but is being increasingly noted later in life. Type 2 diabetes (formerly named non-insulindependent) which results from the body's inability to respond properly to the action of insulin produced by the pancreas.

Type 2 diabetes is much more common and accounts for around 90% of all diabetes cases worldwide. It occurs most frequently in adults, but is being noted increasingly in adolescents as well.

Prevalence of diabetes

In the Eastern Mediterranean Region (as defined by the WHO) there is and estimated 15 million people with diabetes (WHO, 2000). Worldwide it is estimated there are 171 million people with diabetes and this is projected to more than double to 366 million by 2030. Much of this increase will occur in developing countries and will be due to population growth, ageing, unhealthy diets, obesity and sedentary lifestyles.

Treatment

The mainstay of non-pharmacological diabetes treatment is diet and physical activity. About 40% of diabetes sufferers require oral agents for satisfactory blood glucose control, and some 40% need insulin injections. This hormone was isolated by Frederic Banting and Charles Best in 1921 in Canada.

It revolutionized the treatment of diabetes and prevention of its complications, transforming Type 1 diabetes from a fatal disease to one in which long-term survival became achievable. People with Type 1 diabetes are usually totally dependent on insulin injections for survival.

Such people require daily administration of insulin. The majority of people suffering from diabetes have the Type 2 form. Although they do not depend on insulin for survival, about one third of sufferers needs insulin for reducing their blood glucose levels.

Complications

Diabetic retinopathy is a leading cause of blindness and visual disability. Diabetes mellitus is associated with damage to the small blood vessels in the retina, resulting in loss of vision.

Findings, consistent from study to study, make it possible to suggest that, after 15 years of diabetes, approximately 2% of people become blind, while about 10% develop severe visual handicap. Loss of vision due to certain types of glaucoma and cataract may also be more common in people with diabetes than in those without the disease.

Diabetes is among the leading causes of kidney failure, but its frequency varies between populations and is also related to the severity and duration of the disease. Several measures to slow down the progress of renal damage have been identified.

They include control of high blood glucose, control of high blood pressure, intervention with medication in the early stage of kidney damage, and restriction of dietary protein. Screening and early detection of diabetic kidney disease are an important means of prevention.

Heart disease accounts for approximately 50% of all deaths among people with diabetes in industrialized countries. Risk factors for heart disease in people with diabetes include smoking, high blood pressure, high serum cholesterol and obesity. Diabetes negates the protection from heart disease which premenopausal women without diabetes experience. Recognition and management of these conditions may delay or prevent heart disease in people with diabetes.

Diabetic neuropathy is probably the most common complication of diabetes. Studies suggest that up to 50% of people with diabetes are affected to some degree. Major risk factors of this condition are the level and duration of elevated blood glucose. Neuropathy can lead to sensory loss and damage to the limbs. It is also a major cause of impotence in diabetic men. Diabetic foot disease, due to changes in blood vessels and nerves, often leads to ulceration and subsequent limb amputation.

It is one of the most costly complications of diabetes, especially in communities with inadequate footwear. It results from both vascular and neurological disease processes. Diabetes is the most common cause of non-traumatic amputation of the lower limb, which may be prevented by regular inspection and good care of the foot.

Prevention

According to the WHO Large, population-based studies in China, Finland and USA have recently demonstrated the feasibility of preventing, or delaying, the onset of diabetes in overweight subjects with mild glucose intolerance (IGT). The studies suggest that even moderate reduction in weight and only half an hour of walking each day reduced the incidence of diabetes by more than one half.