Practical strategies for improving outcomes in T2DM: The potential role of pioglitazone and DPP4 inhibitors

Abstract

T2DM is a complex disease underlined by multiple pathogenic defects responsible for the development and progression of hyperglycaemia. Each of these factors can now be tackled in a more targeted manner thanks to glucose‐lowering drugs that have been made available in the past 2 to 3 decades. Recognition of the multiplicity of the mechanisms underlying hyperglycaemia calls for treatments that address more than 1 of these mechanisms, with more emphasis placed on the earlier use of combination therapies. Although chronic hyperglycaemia contributes to and amplifies cardiovascular risk, several trials have failed to show a marked effect from intensive glycaemic control. During the past 10 years, the effect of specific glucose‐lowering agents on cardiovascular risk has been explored with dedicated trials. Overall, the cardiovascular safety of the new glucose‐lowering agents has been proven with some of the trials summarized in this review, showing significant reduction of cardiovascular risk. Against this background, pioglitazone, in addition to exerting a sustained glucose‐lowering effect, also has ancillary metabolic actions of potential interest in addressing the cardiovascular risk of T2DM, such as preservation of beta‐cell mass and function. As such, it seems a logical agent to combine with other oral anti‐hyperglycaemic agents, including dipeptidyl peptidase‐4 inhibitors (DPP4i). DPP4i, which may also have a potential to preserve beta‐cell function, is available as a fixed‐dose combination with pioglitazone, and could, potentially, attenuate some of the side effects of pioglitazone, particularly if a lower dose of the thiazolidinedione is used. This review critically discusses the potential for early combination of pioglitazone and DPP4i.

Effects of Pioglitazone on Glucose-Dependent Insulinotropic Polypeptide–Mediated Insulin Secretion and Adipocyte Receptor Expression in Patients With Type 2 Diabetes

“…Emerging therapies using direct GLP-1 and GIP agonists will benefit greatly from a more thorough understanding of extrapancreatic incretin biology. Our results suggest the potential for synergy of TZD and incretin agonist therapy (47).…”

Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

“…Vascular lesions induced by DM often cause pathological changes to the tissues and organs (6). Blood vessels transport blood, secreting bioactive substances, regulating blood pressure and maintaining tissue and organ perfusion (7). It has been demonstrated that microvascular lesions cause diabetic ophthalmopathy and nephropathy and that DM-induced vascular injuries are a key factor in the development of microvascular lesions (8).…”

Metformin and sitagliptin combination therapy ameliorates polycystic ovary syndrome with insulin resistance through upregulation of lncRNA H19

“…Other side effects such as edema [21] and bone fractures [22] were also related to the use of pioglitazone. In a previous study, TECOS in adjunct to DMBG prevented weight regain more effectively than DMBG alone in obese women with PCOS previously treated with liraglutide [6].…”