Abstract
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 antihyperglycemic drugs from the aspect of gut, microbiota, hormones, β cell function, central nervous system, and other cellular mechanisms.
Highlights
Type 2 diabetes mellitus (T2DM) is the commonest type of diabetes mellitus in most economically developed nations
This study suggests that metformin-induced glucagon-like peptide-1 (GLP-1) release may not directly act on islet insulin secretion or via dipeptidyl peptidase-IV (DPP-IV) inhibition
Other studies have reported that chronic administration of acarbose significantly increased FGF21 levels whereas insulin-like growth factor-I (IGF-I) simultaneously decreased in serum, and this could be responsible for the observed extended lifespans in rodents [41]
Summary
Type 2 diabetes mellitus (T2DM) is the commonest type of diabetes mellitus in most economically developed nations. According to the epidemic report by the International Diabetes Federation (IDF) published in 2017, there are an estimated 425 million people currently affected by diabetes. To effectively control the high burden of diabetic nephropathy, coronary heart disease, and stroke in diabetic patients, new antidiabetic medications should be developed through preclinical and clinical research. Many antidiabetic drugs have been put into the market and several others are in the development pipeline most of which have shown good clinical benefits. Some of such drugs include incretin-based therapies and sodium-glucose cotranspotor-2 inhibitors (SGLT-2i). We provide knowledge that can be used to guide the formulation of optimal treatment combinations for clinical management of T2DM
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