Recombinant DNA Technology in the Treatment of Diabetes: Insulin Analogs
Zoltan Vajo,
Janet Fawcett and
William C. Duckworth
Section of Endocrinology, VA Medical Center, Phoenix,
Arizona 85012
Correspondence: Address all correspondence and requests for reprints to: William C. Duckworth, Section of Endocrinology, VA Medical Center, 650 East Indian School Road, 111E, Phoenix, Arizona 85012. E-mail:
william.duckworth{at}med.va.gov
After more than half a century of treating diabetics with animal
insulins,recombinant DNA technologies and advanced protein chemistry
madehuman insulin preparations available in the early 1980s. Asthe
next step, over the last decade, insulin analogs were constructedby
changing the structure of the native protein with the goalof improving
the therapeutic properties of it, because the pharmacokinetic
characteristicsof rapid-, intermediate-, and long-acting preparations
of humaninsulin make it almost impossible to achieve sustained
normoglycemia.The first clinically available insulin analog, lispro,
confirmedthe hopes by showing that improved glycemic control can be
achievedwithout an increase in hypoglycemic events. Two new insulin
analogs,insulin glargine and insulin aspart, have recently been
approvedfor clinical use in the United States, and several other
analogsare being intensively tested. Thus, it appears that a rapid
accelerationof basic and clinical research in this arena will be seen,
whichwill have direct significance to both patients and their
physicians.The introduction of new short-acting analogs and the
developmentof the first truly long-acting analogs and the development
ofanalogs with increased stability, less variability, and perhaps
selectiveaction, will help to develop more individualized treatment
strategiestargeted to specific patient characteristics and to achieve
furtherimprovements in glycemic control. Data on the currently
availableand tested analogs, as well as data on those currently being
developed,are reviewed.
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