An Update on the Effect of Incretin-Based Therapies on β-Cell Function and Mass

Abstract

Type 2 diabetes mellitus (T2DM) is a multifactorial disease with a complex and progressive pathogenesis. The two primary mechanisms of T2DM pathogenesis are pancreatic β-cell dysfunction and insulin resistance. Pancreatic β-cell dysfunction is recognized to be a prerequisite for the development of T2DM. Therapeutic modalities that improve β-cell function are considered critical to T2DM management; however, blood glucose control remains a challenge for many patients due to suboptimal treatment efficacy and the progressive nature of T2DM. Incretin-based therapies are now the most frequently prescribed antidiabetic drugs in Korea. Incretin-based therapies are a favorable class of drugs due to their ability to reduce blood glucose by targeting the incretin hormone system and, most notably, their potential to improve pancreatic β-cell function. This review outlines the current understanding of the incretin hormone system in T2DM and summarizes recent updates on the effect of incretin-based therapies on β-cell function and β-cell mass in animals and humans.

Efficacy and safety of gemigliptin, a dipeptidyl peptidase‐4 inhibitor, in patients with type 2 diabetes mellitus inadequately controlled with combination treatment of metformin and sulphonylurea: a 24‐week, multicentre, randomized, double‐blind, placebo‐controlled study (TROICA study)

“…These drugs increase the concentration of the active form of incretin hormones, such as GLP-1 and glucose-dependent insulinotropic polypeptide, and enhance their biological actions, including glucose-dependent insulin secretion, suppression of glucagon secretion, improvement of pancreatic β-cell function, and may be able to preserve β-cell mass. [8][9][10] In addition, DPP-4 inhibitors have a neutral effect on weight and have a low risk of hypoglycaemia when used as monotherapy. 1 Based on these advantages, DPP-4 inhibitors represent a rational choice as a third agent for use in combination with metformin and sulphonylurea.…”

Efficacy and safety of adding evogliptin versus sitagliptin for metformin‐treated patients with type 2 diabetes: A 24‐week randomized, controlled trial with open label extension

“…Pancreatic β‐cell dysfunction is one of the primary mechanisms of T2DM pathogenesis . Therefore, the modalities used to improve β‐cell function are a critical aspect of T2DM management.…”

“…In this phase III, randomized, double-blind, active-controlled study we proved that adding evogliptin or sitagliptin for inadequately con- Pancreatic β-cell dysfunction is one of the primary mechanisms of T2DM pathogenesis. 15 Therefore, the modalities used to improve β-cell function are a critical aspect of T2DM management. In our study, β-cell function was estimated by HOMA-β, and evogliptin improved HOMA-β by 11.36% AE 27.92% (P < .0001) at week 24 and it was not different from the improvement with sitagliptin (11.82% AE 29.43%, P < .0001).…”

Recent Advances in Effect‐directed Enzyme Assays based on Thin‐layer Chromatography

“…DPP-4 is responsible for the rapid degradation of GLP-1 and GIP by cleaving preferentially peptides with a proline or alanine residue in the second aminoterminal position (Biftu et al, 2007;Richter et al, 2008;Wong et al, 2014;Chon and Gautier, 2016). DPP-4 inhibitors increase circulating levels of active incretin hormones and exert a glucose-dependent action on β-cell function, triggering insulin and suppressing glucagon secretion under hyperglycemic conditions (Barnett, 2006;Wong et al, 2014;Chon and Gautier, 2016). DPP-4 inhibitors are well-tolerated and unlikely to cause adverse effects such as hypoglycaemia, body-weight gain or gastrointestinal side-effects typically associated with other agents (Biftu et al, 2007;Deacon and Lebovitz, 2016).…”