Insulin analogues.

N Engl J Med 2005;352:174-83. Copyright © 2005 Massachusetts Medical Society. he discovery of insulin more than 80 years ago is considered one of the greatest medical breakthroughs of the 20th century. 1 The first commercial insulin preparations contained numerous impurities and varied in potency from lot to lot by as much as 25 percent. Manufacturing techniques improved rapidly, however, which allowed the production of higher-quality formulations from bovine and porcine sources. In the 1930s, the first long-acting preparation, protamine zinc insulin, was developed to reduce the number of injections necessary for adequate insulin replacement. 2 This preparation was often used once daily, without the addition of regular insulin, which set a trend that lasted through the 1950s, when neutral protamine Hagedorn (NPH) and insulin zinc (Lente) were introduced. In the ensuing two decades, a movement toward more complete coverage of insulin requirements resulted in the twice-daily “split-mix” regimen of NPH and regular insulin that is used to this day. 3