Recombinant DNA technology in the treatment of diabetes: Insulin analogs

After more than half a century of treating diabetics with animal insulins, recombinant DNA technologies and advanced protein chemistry made human insu lin preparations available in the early 1980s. As the next step, over the l ast decade, insulin analogs were constructed by changing the structure of t he native protein with the goal of improving the therapeutic properties of it, because the pharmacokinetic characteristics of rapid-, intermediate-, a nd long-acting preparations of human insulin make it almost impossible to a chieve sustained normoglycemia. The first clinically available insulin anal og, lispro, confirmed the hopes by showing that improved glycemic control c an be achieved without an increase in hypoglycemic events. Two new insulin analogs, insulin glargine and insulin aspart, have recently been approved f or clinical use in the United States, and several other analogs are being i ntensively tested. Thus, it appears that a rapid acceleration of basic and clinical research in this arena will be seen, which will have direct signif icance to both patients and their physicians. The introduction of new short -acting analogs and the development of the first truly long-acting analogs and the development of analogs with increased stability, less variability, and perhaps selective action, win help to develop more individualized treat ment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control. Data on the currently available and tested analogs, as well as data on those currently being developed, are reviewed.