Abstract
This chapter presents the recent advances in therapeutic approaches to type 2 diabetes (T2D). The developments discussed in this chapter, can be broadly classified into (1) enhancers of insulin release, (2) enhancers of insulin action, (3) inhibitors of hepatic glucose production, and (4) inhibitors of glucose absorption from the gut. Major current therapies for T2D include sulfonylureas, metformin, and TZDs. Each of these therapies has limitations with regard to their efficacy or side-effect profile. Among the targets discussed in this chapter, the most advanced are those based on glucagon-like peptide 1 (GLP-1) agonist activity—that is, Exenatide, and DPPIV (dipeptidyl peptidase IV )inhibitors. Both strategies are directed to potentiate the actions of GLP-1 on insulin secretion and have shown promise in Phase II/III clinical trials. These agents may avoid complications related to hypoglycemia and also may limit the potential for weight gain, thus complementing existing therapies. The discovery of potent Protein tyrosine phosphatase 1B (PTP1B) inhibitors remains a challenge; however, progress is being made and effective PTP1B inhibitors are expected to show beneficial effects in reducing insulin resistance and modulating weight gain. Glucokinase activation is the newest strategy disclosed.
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