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Peptide Drug Design for Diabetes and Related Metabolic Diseases

  • Niels C. KaarsholmEmail author
Chapter

Abstract

This chapter reviews the major peptide modalities used in the treatment of diabetes and related metabolic disorders. The focus is on design principles for molecules and formulations in current and emerging applications. Insulin is by far the largest single category. Traditional and ongoing efforts on engineering predictable pharmacokinetic (PK) profiles have gradually refined the injectable insulin preparations we know today. A set of innovations for the future focus on ways to circumvent the intrinsic low therapeutic index of insulin, either by developing a glucose-responsive insulin or a “closed-loop” delivery system capable of operating as an artificial pancreas. Only discovered in the 1980’s, glucagon-like peptide-1 (GLP-1) is already established as an important and rapidly growing diabetes drug class. A variety of peptide engineering techniques have been used to develop GLP-1 analogs with a wide range of PK properties. The combination of glucose-dependent insulin release and the central effect on satiety makes GLP-1 particularly attractive in the treatment of type 2 diabetes, alone or together with insulin. Emerging combinations of the anorectic GLP-1 effect with a boost in energy expenditure or other pharmacologies currently seek to explore applications in co-morbidities such as obesity.

Keywords

Diabetes mellitus Pharmacotherapy Drug design Incretins Peptides Glucagon-like peptide-1 Insulin 

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Managing Consultant at N.C. Kaarsholm, LLCCopenhagenDenmark

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