Endocrine Abstracts (2011) 26 S15.3

Future therapies - what is in the pipeline?

Signe Sørensen Torekov

University of Copenhagen, Copenhagen, Denmark.

Incretin-based therapies, such as the injectable GLP-1 receptor agonists and orally administered DPP-4 inhibitors, have recently been introduced into clinical practice. At present, the GLP-1 receptor agonists need to be administered once or twice daily. Several once weekly GLP-1 receptor agonists are in phase 3 development. This review examines the efficacy, safety and perspective for the future of the once weekly GLP-1 receptor agonists: exenatide once weekly, taspoglutide, albiglutide, LY2189265 and CJC-1134-PC and compare them to the currently available agonists, exenatide BID and liraglutide QD. A greater reduction in HbA1c and fasting plasma glucose was found with the once weekly GLP-1 receptor agonists compared with exenatide BID, while the effect on postprandial hyperglycemia was modest with the once weekly GLP-1 receptor agonist. The reduction in HbA1c was in most studies greater compared to oral antidiabetic drugs and insulin glargine. The reduction in weight did not differ between the short and long acting agonists. The gastrointestinal side effects were less with the once weekly agonists compared with exenatide BID, except for taspoglutide. Antibodies seem to be most frequent with exenatide once weekly, while hypersensitivity has been described in few patients treated with taspoglutide. Injection site reactions differ among the long acting GLP-1 receptor agonists and are observed more frequently than with exenatide BID and liraglutide. In humans no signal has been found indicating an association between the once weekly agonists and C-cell cancer. The cardiovascular safety, durability of glucose control and effect on weight will emerge from several ongoing major long-term trials. The once weekly GLP-1 receptor analogues are promising candidates for the treatment of type 2 diabetes although their efficacy may not be superior to once daily analogue liraglutide.

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