Detailed Study on the Mechanism of Metabolic Influences on the Endogenous GLP-1 by Oral Antidiabetic Medications in Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is now the commonest type of diabetes mellitus in most
economically developed nations. Incretin-based therapy is now a prevalent treatment option for
patients with type 2 diabetes mellitus (T2DM). It has been associated with considerably good results
in the management of hyperglycemia with cardiac or nephron-benefits. For this reason, it is
recommended for individuals with cardiovascular diseases in many clinical guidelines. As an incretin
hormone, glucagon-like peptide-1 (GLP-1) possesses multiple metabolic benefits such as optimizing
energy usage, maintaining body weight, β cell preservation, and suppressing neurodegeneration.
However, recent studies indicate that oral antidiabetic medications interact with endogenous or
exogenous GLP-1. Since these drugs are transported to distal intestine portions, there are concerns
whether these oral drugs directly stimulate intestinal L cells which release GLP-1, or whether they do
so via indirect inhibition of the activity of dipeptidyl peptidase- IV (DPP-IV). In this review, we discuss
the metabolic relationships between oral anti-hyperglycemic drugs from the aspect of gut, microbiota,
hormones, β cell function, central nervous system, and other cellular mechanisms. The findings of
these studies provide the rationale for the development of new drugs or formulations, which can
ensure better glucose metabolism.