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- W1544903325 abstract "The incidence of type 2 diabetes in developed countries is increasing yearly with a significant negative impact on patient quality of life and an enormous burden on the healthcare system. Current biguanide and thiazolidinedione treatments for type 2 diabetes have a number of clinical limitations, the most serious long‐term limitation being the eventual need for insulin replacement therapy (Table 1). Since 2007, drugs targeting the glucagon‐like peptide‐1 ( GLP ‐1) receptor have been marketed for the treatment of type 2 diabetes. These drugs have enjoyed a great deal of success even though our underlying understanding of the mechanisms for their pleiotropic effects remain poorly characterized even while major pharmaceutical companies actively pursue small molecule alternatives. Coupling of the GLP ‐1 receptor to more than one signalling pathway (pleiotropic signalling) can result in ligand‐dependent signalling bias and for a peptide receptor such as the GLP ‐1 receptor this can be exaggerated with the use of small molecule agonists. Better consideration of receptor signalling pleiotropy will be necessary for future drug development. This is particularly important given the recent failure of taspoglutide, the report of increased risk of pancreatitis associated with GLP ‐1 mimetics and the observed clinical differences between liraglutide, exenatide and the newly developed long‐acting exenatide long acting release, albiglutide and dulaglutide. Linked Articles This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2014.171.issue‐5" @default.
- W1544903325 created "2016-06-24" @default.
- W1544903325 creator A5031351126 @default.
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- W1544903325 creator A5049639665 @default.
- W1544903325 creator A5050817719 @default.
- W1544903325 creator A5078874300 @default.
- W1544903325 date "2014-02-27" @default.
- W1544903325 modified "2023-10-14" @default.
- W1544903325 title "Molecular mechanisms underlying physiological and receptor pleiotropic effects mediated by <scp>GLP</scp>‐<scp>1R</scp> activation" @default.
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