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Vol. 52, Issue 1, 1-10, March 2000

Genetically Engineered Insulin Analogs: Diabetes in the New Millenium

Zoltan Vajo and William C. Duckworth1

Section of Endocrinology, Veterans Affairs Medical Center, Phoenix, Arizona

I. Introduction
II. Short-Acting Insulin Analogs
    A. Insulin Asp(B10)
    B. Insulin Lispro
    C. Insulin Aspart
III. Long-Acting Insulin Analogs
    A. NovoSol Basal
    B. HOE 901
    C. Fatty Acid Acylated Insulins
IV. Future Directions
    A. Increased Stability
    B. Less Variability
    C. Selective Action
    D. Ultra Rapid Onset
    E. Ultra Long Activity
    F. Benefit without Metabolic Activity?
V. Closing Thoughts
References

Tight glucose control is essential to minimize complications in diabetic patients. However, the pharmacokinetic characteristics of the currently available rapid-, intermediate-, and long-acting preparations of human insulin make it almost impossible to achieve sustained normoglycemia. Until recently, improvements in insulin formulations were seriously limited as advances were only achieved in insulin purity, species, and characteristics of the retarding agent. The availability of molecular genetic techniques opened new windows to create insulin analogs by changing the structure of the native protein and to improve the therapeutic properties. The first clinically available insulin analog, Lispro, confirmed the hopes by showing that improved glycemic control can be achieved without an increase in hypoglycemic events. This requires, however, optimal basal insulin replacement, either by multiple daily injections of neutral protein Hagedorn (NPH) insulin or by insulin pump. Evidence suggests that short-acting insulin analogs would be better matched by a true basal insulin than by the erratically absorbed and rather short-acting NPH insulin. Therefore, future availability of long-acting analogs raises the hope to realize the true potential benefits of the currently available short-acting analog, Lispro, and of those still awaiting approval. The introduction of new short-acting and the first truly long-acting analogs, the development of analogs with increased stability, less variability and perhaps selective action will help to develop more individualized treatment strategies targeted to specific patient characteristics and to achieve further improvements in glycemic control.


1 Address for correspondence: William C. Duckworth, Section of Endocrinology, Veterans Affairs Medical Center, 650 E. Indian School Rd., 111E, Phoenix, AZ 85012.


0031-6997/00/5201-0001$03.00/0
PHARMACOLOGICAL REVIEWS
Copyright © 2000 by The American Society for Pharmacology and Experimental Therapeutics



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