Dataset Information

Incretin agents in type 2 diabetes.

ABSTRACT:

Objective

To evaluate the emerging classes of antihyperglycemic agents that target the incretin pathway, including their therapeutic efficacy and side effect profiles, in order to help identify their place among the treatment options for patients with type 2 diabetes.

Quality of evidence

MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched. Most evidence is level I and II.

Main message

Two classes of incretin agents are currently available: glucagonlike peptide 1 (GLP1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, both of which lower hyperglycemia considerably without increasing the risk of hypoglycemia. The GLP1 receptor agonists have a greater effect on patients' glycated hemoglobin A(1c) levels and cause sustained weight loss, whereas the DPP4 inhibitors are weight-neutral.

Conclusion

The GLP1 and DPP4 incretin agents, promising and versatile antihyperglycemic agents, are finding their way into the therapeutic algorithm for treating type 2 diabetes. They can be used in patients not adequately controlled by metformin monotherapy or as initial therapy in those for whom metformin is contraindicated.

SUBMITTER: Ross SA

PROVIDER: S-EPMC2922799 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Incretin agents in type 2 diabetes.

Ross Stuart A SA Ekoé Jean-Marie JM

Canadian family physician Medecin de famille canadien 20100701 7

<h4>Objective</h4>To evaluate the emerging classes of antihyperglycemic agents that target the incretin pathway, including their therapeutic efficacy and side effect profiles, in order to help identify their place among the treatment options for patients with type 2 diabetes.<h4>Quality of evidence</h4>MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews were searched. Most evidence is level I and II.<h4>Main message</h4>Two classes of incretin agents are currently available: glucago ...[more]

PMID: 20631270

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Project description:Incretin hormones (glucose-dependent insulinotropic polypeptide [GIP] and glucagon-like peptide-1 [GLP-1]) play a role in the pathophysiology of type 2 diabetes. Along with their derivatives they have shown therapeutic success in type 2 diabetes, with the potential for further improvements in glycaemic, cardiorenal and body weight-related outcomes. In type 2 diabetes, the incretin effect (greater insulin secretory response after oral glucose than with 'isoglycaemic' i.v. glucose, i.e. with an identical glycaemic stimulus) is markedly reduced or absent. This appears to be because of a reduced ability of GIP to stimulate insulin secretion, related either to an overall impairment of beta cell function or to specific defects in the GIP signalling pathway. It is likely that a reduced incretin effect impacts on postprandial glycaemic excursions and, thus, may play a role in the deterioration of glycaemic control. In contrast, the insulinotropic potency of GLP-1 appears to be much less impaired, such that exogenous GLP-1 can stimulate insulin secretion, suppress glucagon secretion and reduce plasma glucose concentrations in the fasting and postprandial states. This has led to the development of incretin-based glucose-lowering medications (selective GLP-1 receptor agonists or, more recently, co-agonists, e.g. that stimulate GIP and GLP-1 receptors). Tirzepatide (a GIP/GLP-1 receptor co-agonist), for example, reduces HbA1c and body weight in individuals with type 2 diabetes more effectively than selective GLP-1 receptor agonists (e.g. semaglutide). The mechanisms by which GIP receptor agonism may contribute to better glycaemic control and weight loss after long-term exposure to tirzepatide are a matter of active research and may change the pessimistic view that developed after the disappointing lack of insulinotropic activity in people with type 2 diabetes when exposed to GIP in short-term experiments. Future medications that stimulate incretin hormone and other receptors simultaneously may have the potential to further increase the ability to control plasma glucose concentrations and induce weight loss.

Project description:Type 2 diabetes in East Asians is characterized primarily by β-cell dysfunction, and with less adiposity and less insulin resistance compared with that in Caucasians. Such pathophysiological differences can determine the appropriate therapeutics for the disease. Incretins, glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1, are secreted in response to meal ingestion, and enhance insulin secretion glucose-dependently. Incretin-based drugs, dipeptidyl peptidase-4 inhibitors (DPP-4i) and glucagon-like peptide-1 receptor agonists, that ameliorate β-cell dysfunction with limited hypoglycemia risk are now widely used in type 2 diabetes management. Recent meta-analyses of clinical trials on DPP-4i and glucagon-like peptide-1 receptor agonists found that the drugs were more effective in Asians, most likely because of amelioration of β-cell dysfunction. In addition, we found increased glycated hemoglobin-lowering effects of DPP-4i to be associated with intake of fish in type 2 diabetes, which suggests that dietary customs of East Asians might also underlie the greater efficacy of DPP-4i. Despite the limited risk, cases of severe hypoglycemia were reported for DPP-4i/sulfonylureas combinations. Importantly, hypoglycemia was more frequent in patients also receiving glibenclamide or glimepiride, which activate exchange protein directly activated by cyclic adenosine monophosphate 2, a critical mediator of incretin signaling, and was less frequent in patients receiving gliclazide, which does not activate exchange protein directly activated by cyclic adenosine monophosphate 2. Prevention of insulin-associated hypoglycemia by DPP-4i has gained attention with regard to the enhancement of hypoglycemia-induced glucagon secretion by insulinotropic polypeptide, but remains to be investigated in East Asians. Despite the safety issues, which are paramount and must be carefully monitored, the incretin-based drugs could have potential as a first choice therapy in East Asian type 2 diabetes patients.

Dataset Information

Incretin agents in type 2 diabetes.

Objective

Quality of evidence

Main message

Conclusion

Publications

Incretin agents in type 2 diabetes.

Similar Datasets

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