The Business of Insulin: A Relationship Between Innovation and Economics
Steven B. Leichter, MD, FACP, FACE
nsulin, as a commercial product, is undergoing a substantial metamor- phosis from a commodity item to a potential growth vehicle for its manufac- turers. This trend has accelerated during the past 5 years with the introduction of a growing number of insulin analogs and novel insulin injection devices. I
Although this innovation has, of course, been presented as improved medical therapy, the business aspects of the insulin market suggest that the eco- nomic rewards are important drivers of these developments. The trends in eco- nomic data prophesize that business con- siderations may enhance the pace of innovation and may lead to the elimina- tion of traditional insulin products in favor of more profitable analogs.
Whether the clinical benefits of these trends justify the economic costs should be analyzed. Therefore, a consideration of the trends in the insulin market is clearly in order.
Innovations in Insulin Since 1980 From the clinical discovery and wide- spread application of insulin in the early 1920s, insulin products did not undergo major changes until 1980. Before then, insulin was partially purified from pig or cow pancreases. Much of the commer- cial insulin sold in the United States had relatively large levels of impurities. Therefore, patients on insulin therapy often developed antibodies to the impu- rities in the product and to the animal insulin itself.1 In most instances, these antibodies functioned as “blocking anti- bodies,” which inactivated part of the administered doses and caused reduced glycemic control. In some cases, true
allergic reactions occurred from the anti- genic process.
As the 1980s dawned, two related trends improved the purity and reliability of commercial insulin. The impending release of purified, genetically engi- neered, biosynthetic human insulin by Eli Lilly and Co. caused the introduction of highly purified pork insulin products by Novo Nordisk Pharmaceuticals, Inc. Novo recognized that its human insulin product would be introduced later than that of Lilly, so it attempted to retain market presence with its purified pork insulins. Pork insulin was much less antigenic than beef insulin, and highly purified insulin preparations were much less antigenic than the products that had been sold to that point.2 The resulting market emphasis on purified pork or human insulins caused a fairly rapid reduction in the use of impure insulins and beef insulins.
In June 1982, Lilly marketed the first biosynthetic human insulin. The first patient to be treated with this product illustrated its potential therapeutic bene- fits.3 He was an 18-year-old college stu- dent with type 1 diabetes, who had poor glycemic control despite a progressive increase in daily insulin dose from 50 to >110 units. Anti-insulin antibody titers
Table 1. Insulin Analogs
Insulin lispro (Eli Lilly and Co.) Insulin aspart (Novo Nordisk
Pharmaceuticals, Inc.) Insulin glargine (Aventis)
Insulin detemir (Novo Nordisk Pharmaceuticals, Inc.)
in this young man were extremely high, explaining the apparent ineffectiveness of his insulin therapy. Two days after he was started on human insulin, his daily insulin dosage had to be reduced to 65 units, suggesting that he was no longer generating the same titers of anti-insulin antibodies.
Although growth of human insulin sales was initially modest, this product line became the predominant insulin group by the mid-1990s. By 2000, both major manufacturers discontinued wide- spread sales of animal insulins.4
Innovations in Insulin Therapy Starting in the mid-1990s, specifically modified insulins, again made through biosynthetic technology, were intro- duced. These insulin analogs are “designer insulins,” with protein struc- tures modified to achieve specific thera- peutic goals (Table 1). The first to be introduced, insulin lispro (Humalog) appeared in 1996. It has been advocated as a product that mimics the postprandi- al action of endogenous, human insulin better than standard, biosynthetic human regular insulin.5
Another vehicle for growth in the insulin marketplace has been the intro- duction of new injection devices for
Rapid time course of action Rapid time course of action
24-hour time course of action
without “peak” actions Long-acting insulin analog
Volume 21, Number 1, 2003 • CLINICAL DIABETES