An overview of once‐weekly glucagon‐like peptide‐1 receptor agonists—available efficacy and safety data and perspectives for the future

Jan 7, 2011Diabetes, obesity & metabolism

Overview of once-weekly glucagon-like peptide-1 medicines: effectiveness, safety, and future outlook

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Abstract

A greater reduction in haemoglobin A1c (HbA1c) and fasting plasma glucose was found with once-weekly GLP-1 receptor agonists compared to exenatide BID.

Once-weekly GLP-1 receptor agonists may lead to superior reductions in HbA1c and fasting plasma glucose compared to short-acting options.
The effect on postprandial hyperglycaemia is modest with once-weekly GLP-1 receptor agonists.
Weight reduction did not differ between short-acting and long-acting agonists.
Gastrointestinal side effects were less frequent with once-weekly agonists compared to exenatide BID, except for taspoglutide.
Injection site reactions were more common with long-acting GLP-1 receptor agonists than with exenatide BID and liraglutide.
No association has been found between once-weekly agonists and C-cell cancer in humans.

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Incretin-based therapies, such as the injectable glucagon-like peptide-1 (GLP-1) receptor agonists and orally administered dipeptidyl peptidase-4 (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 compared them to the currently available agonists, exenatide BID and liraglutide QD. A greater reduction in haemoglobin A1c (HbA1c) and fasting plasma glucose was found with the once-weekly GLP-1 receptor agonists compared with exenatide BID, while the effect on postprandial hyperglycaemia 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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An overview of once‐weekly glucagon‐like peptide‐1 receptor agonists—available efficacy and safety data and perspectives for the future

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