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Diabetes mellitus (DM) is a risk factor for cancer in many organs and associated with an increased risk of cholangiocarcinoma (CCA). The molecular linkage between these diseases has been demonstrated in preclinical studies, which have highlighted the role of hyperinsulinemia and hyperglycemia in the carcinogenesis and progression of CCA. Recent studies on the emerging role of antidiabetic medication in the development and progression of CCA showed a subclass of antidiabetic drug with a therapeutic effect on CCA. Although associations between CCA, insulin analogues and sulfonylureas are unclear, incretin-based therapy is likely associated with an increased risk for CCA, and may lead to CCA progression, as demonstrated by in vitro and in vivo experiments. In contrast, biguanides, especially metformin, exert an opposite effect, associated with a reduced risk of CCA and inhibited in vitro and in vivo CCA progression. The association between incretin-based therapy and the risk of CCA needs further clarification, as metformin is being studied in an ongoing clinical trial. Understanding the association between DM and CCA is critical for preventing the development of CCA in patients with DM, and for establishing the appropriateness of antidiabetic medication to treat CCA. Determining how metformin affects CCA can lead to repurposing this safe and well-known drug for improving CCA treatment, regardless of the diabetes status of patients., (Copyright © 2020 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

The consumption of non-nutritive, low, or no-calorie sweeteners (LCS) is increasing globally. Previously thought to be physiologically inert, there is a growing body of evidence that LCS not only provide a sweet taste but may also elicit metabolic effects in the gastrointestinal tract. This review provides a brief overview of the chemical and receptor-binding properties and effects on chemosensation of different LCS but focuses on the extent to which LCS stimulates glucose transport, incretin and insulin secretion, and effects on glucose tolerance. Aspartame and sucralose both bind to a similar region of the sweet receptor. For sucralose, the data are contradictory regarding effects on glucose tolerance in humans and may depend on the food or beverage matrix and the duration of administration, as suggested by longer term rodent studies. For aspartame, there are fewer data. On the other hand, acesulfame-potassium (Ace-K) and saccharin have similar binding characteristics to each other but, while Ace-K may increase incretin secretion and glucose responses in humans, there are no data on saccharin except in rats, which show impaired glucose tolerance after chronic administration. Additional research, particularly of the effects of chronic consumption, is needed to provide concrete evidence for beneficial or detrimental effects of LCS on blood glucose regulation in humans.

Recent years have seen an enormous increase in the number of therapeutic agents available for lowering blood glucose levels in people with type 2 diabetes. Among these agents, the incretin mimetics glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists and dipeptidyl peptidase 4 (DPP4) inhibitors have received particular attention for the potential of these interventions to positively impact on cardiovascular outcomes. Although the results of large-scale cardiovascular outcome trials eagerly are anticipated, an increasing body of literature from preclinical and early phase clinical studies has indicated that both GLP-1R agonists and DPP4 inhibitors may exert glucose-independent cardiovascular effects. Despite its role in glucose homeostasis, the GLP-1R is surprisingly widely distributed throughout the body, including in the heart. GLP-1 may exert its effects through both receptor-dependent and receptor-independent mechanisms and through the actions of both the intact peptide and its metabolites. In addition, DPP4 inhibition not only augments the circulating levels of incretin hormones, but it also holds the capacity to augment the activity of other biologically important substrates, most notably the small protein stromal cell-derived factor 1 alpha. Whether these collective functions will act to reduce cardiovascular events in patients remains to be determined., (Copyright © 2013 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

For the treatment of T2DM; cure can not be achieved with conventional methods. The degree of increase in the epidemic of diabetes; together with the research of new treatments will provide a better understanding of patophysiology necessitates the development. Preferred drugs in cases that do not respond to metformin; hypoglycemia, can cause weight gain and are undesirable cardiac event. Today; incretin-based therapies have been developed that provide effective glucose level and weight control. Incretins while increasing glucose dependent insulin secretion in the pancreas, suppress glucagon secretion. Glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors, are incretin based treatment. Glucagon-like peptide-1 receptor agonists is the most important treatment can be used with monotherapy or combination therapy. Glucagon-like peptide-1 agonists, besides providing good glycemic control, the low rate of hypoglycemia and weight loss are causing significant advantage. Dipeptidyl peptidase-4 inhibitors; leads to rapid inactivation of incretin hormones such as glucagon-like peptide-1 agonists and glucose dependent insulinotropic polypeptide. Dipeptidyl peptidase-4 inhibitors; they extend the duration of action of glucagon-like peptide-1 by inhibiting the degradation of incretin hormones in circulation. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a chronic illness that requires continuing medical care and multifactorial strategies to reduce the risk of long-term complications. Antihyperglycemic agents are directed towards one or more of the pathophysiological defects of type 2 diabetes, or modify physiological processes relating to appetite or to nutrient absorption. In recent years, incretin-based therapies such as glucagon like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 inhibitors (DPP-4) have become important therapeutic options for treatment of type 2 diabetes. In addition to the proven glucose-lowering efficacy, the incretin agents have numerous extraglycaemic effects that could translate into potential cardiovascular and other benefits. Available data suggest that incretin-based therapies could prevent cardiovascular disease via multiple mechanisms. Longer-term trials designed to assess the effect on major cardiovascular events are currently ongoing. [ABSTRACT FROM AUTHOR]