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Pharmacologic modifications of hormones to improve their therapeutic potential for diabetes management

Rapid‐acting genetically engineered insulin analogues emerging in the last 10 years are now established as more effective prandial insulins than traditional short‐acting human insulin. The development of analogues for use as basal insulin, however, has been much slower. Methods of protracting the time–action curve of injected insulin include complexing with proteins, insulin crystal formation, shifting the iso‐electric point of the amino acid sequence or attaching a fatty‐acid side chain to the molecule. The latter two methods have been more successful in producing physiologic insulin profiles when compared with the former methods. The principle of acylation has also been applied to prolong the action of other hormones, such as glucagon‐like peptide 1 (GLP‐1), as the native peptide has a very short half‐life. Preliminary results with this compound and other GLP‐1 analogues show promise in treating patients with type 2 diabetes. In summary, the development of new insulin and other hormone preparations by the manipulation of native peptide structure has recently improved our antidiabetic armamentarium, and further research will continue this fruitful approach.