Insulin therapies have evolved to the point where Drs. Frederick Banting and Charles Best would hardly recognize their own discovery. With the advent of modern recombinant DNA technology, scientists have developed insulin analogs that better mimic the body's normal insulin action. Now, more predictable basal and bolus insulin therapies help achieve tighter glucose control.

New insulin products will be reaching pharmacies over the next few months. The first to hit the market by the end of the year will be the rapid-acting insulin Apidra (insulin glulisine, Sanofi-Aventis). The long-acting insulin Levemir (insulin detemir, Novo Nordisk), cleared by the Food & Drug Administration in June, is expected to be available in the first half of next year.

The evolution of insulin is far from over, however. Several promising needle-free therapies, such as inhaled insulin, are in development, and the first inhalable, rapid-acting insulin, Exubera (insulin [rDNA origin] powder for oral inhalation, Pfizer, Sanofi-Aventis), is inching closer to market after a positive recommendation to the FDA in September from an expert committee. Another inhaled insulin product, jointly developed by Eli Lilly and Alkermes, has begun phase III studies.

Diabetes experts speculate that perhaps the future will bring implantable chips that release insulin, or maybe there will be insulin pumps that automatically activate according to the body's need to avoid hypoglycemia.

"The goal in insulin therapy is to mimic nature's insulin pattern; the risk is hypoglycemia. The more you try for optimal control, the more risk of hypoglycemia, and, therefore, the more you need the most precise tools," said Scott Drab, Pharm.D., assistant professor of pharmaceutical sciences at the University of Pittsburgh School of Pharmacy.

With the "designer insulin" therapies offering significant benefits, pharmacists seldom dispense older, longer-acting insulin or the pork-based insulin products anymore. As a result, Lilly announced in July the discontinuation of four insulin agents: Humulin U Ultralente, Humulin L Lente, Regular Iletin II, and NPH Iletin II. The company expects that the products will be available in pharmacies until the end of 2005.

"Over the past few decades there has been a great deal of innovation in insulin therapy, such as rapid-acting analogs, analog mixtures, basal analogs, and other human insulin products and formulations," said Lilly's Scott Jacober, M.D. "As a result, we've seen a significant and steady decline in usage of the products we're discontinuing as doctors continue to move their patients towards newer therapies." In a Dear Doctor letter about Humulin U and Humulin L, Lilly stated that "use of these longer-acting insulins has declined by more than 70% over the past five years due to newer insulin therapies."

According to Lilly, of the 3.5 million patients with diabetes using insulin in the United States, less than 2% will be affected by the discontinuations. Only about 2,000 people use the animal-based products.

Jerry Meece, R.Ph., of Plaza Pharmacy & Wellness Center in Gainesville, Texas, stated that none of his patients are taking these insulin products. "Because diabetes is a highly individualized disease, you are going to find some patients who will say that lente works better, but it's going to be a very small number of people."

Switching insulin treatments

For those pharmacists who still have patients on lente or ultralente insulin products, diabetes experts offer cautionary advice.

Patients may mistake the product discontinuation as a product recall and worry about safety, explained Judy Sommers-Hanson, Pharm.D., CDM, pharmacy care manager at Dominick's Pharmacy in Oakbrook, Ill. "Pharmacists will have to educate patients and help them learn about new products and why they have to change to a different therapy."

Changing patients from one insulin to another is not a simple process, contended Drab. "Some healthcare providers may presume that animal and human insulin therapies can be switched unit per unit," he noted. "That's not necessarily true. Typically, what I have noticed is when you switch from an animal insulin to a human insulin, you tend to require a little bit less insulin. Maybe 10 units or 15 units less are required."