Conclusion

Abstract

Clinical studies have revealed that GLP-1 therapy might be intrinsically safer than insulin therapy because of its glucose dependent action, thus eliminating the chances of hypoglycaemia. This book discusses the prodrug strategy as a means to extend the half life of GLP-1 which otherwise has a very short duration of action. An ideal prodrug should be stable to storage but must convert to the active drug under a specific set of conditions. These conditions for the activation of the prodrug will depend on its purpose and site of action. Detailed stability studies are important for the rigorous characterisation of promising prodrugs. However, a rapid screening helps in the identification of such prodrug candidates. The conditions described for the conversion here are a pH of 7.2 and temperature of 37 °C. These conditions were used for the cleavage of the prodrugs as they are physiologically invariant and can thus be translated into other peptidic drugs as well. The advantages of this strategy are discussed in this chapter. The biggest advantage is that the rate of conversion can be fine-tuned by selecting the structure of the pro-moieties. It is possible that the half lives of these prodrugs might be different when studied in vivo as compared to the in vitro experiments. This will probably be as a result of the action of the esterases and other enzymes, but unlikely a change in the chemical rate of conversion. The studies of the structure of additional pro-moieties and how they affect the rate of conversion will provide additional diversity in prodrug chemistry for future use.