Glycaemic control in type 2 diabetes : targets and new therapies

Type 2 diabetes mellitus (T2DM) is a worldwide public health challenge. Despite the availability of many antidiabetes agents and pharmacotherapies targeting cardiovascular risk factors, the morbidity, mortality and economic consequences of T2DM are still a great burden to patients, society, health care systems and the economy. The need for new therapies for glycaemic control is compounded by the fact that existing treatments have limitations either because of their side effects (particularly weight gain and hypoglycaemia) or contraindications that limit their use. Furthermore, none of the current therapies have a significant impact on disease progression. Incretin-based therapies offer a new therapeutic approach to the management of T2DM, and there are also several even newer therapies in development. There are two groups of incretin-based therapies currently available; dipeptidyl peptidase-4 (DPP-4) inhibitors and GLP-1 analogues/mimetics. The former are given orally while the latter subcutaneously. These drugs result in glucose-dependent insulin secretion and glucose-dependent glucagon suppression, with consequent low risk of hypoglycaemia when used as mono- or combination therapy (except when used with sulphonylureas). In addition, they are either weight neutral in the case of DPP-4 inhibitors or cause weight loss in the case of incretin mimetics/analogues. Furthermore, animal studies have shown that these agents prolong β cell survival which offers the theoretical possibility of slowing the progression to T2DM. In this article we will review the currently available antidiabetes agents with particular emphasis on incretin-based and future therapies. In addition, we will review and discuss the evidence relating to glycaemic control and cardiovascular disease.