Diabetes Obes Metab. 2015 Oct 29. doi: 10.1111/dom.12596. [Epub ahead of print]
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1Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.
Abstract
Currently, six glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for treating type 2 diabetes. These fall into two classes based on their receptor activation: short-acting exenatide twice daily (BID) and lixisenatide once daily (OD); and longer-acting liraglutide OD, exenatide once weekly (OW), albiglutide OW and dulaglutide OW. The phase 3 trial of a seventh GLP-1RA, taspoglutide OW, was stopped due to unacceptable adverse events (AEs). Nine phase 3 head-to-head trials and one large phase 2 study have compared the efficacy and safety of these seven GLP-1RAs. All trials were associated with notable reductions in HbA1c, although liraglutide led to greater decreases than exenatide formulations and albiglutide, and HbA1c reductions did not differ between liraglutide and dulaglutide. As the short-acting GLP-1RAs delay gastric emptying, they have greater effects on postprandial glucose levels than the longer-acting agents, whereas the longer-acting compounds reduced plasma glucose throughout the 24-h period studied. Liraglutide was associated with weight reductions similar to those with exenatide BID but greater than those with exenatide OW, albiglutide and dulaglutide. The most frequently observed AEs with GLP-1RAs were gastrointestinal disorders, particularly nausea, vomiting and diarrhoea; nausea, however, occurred less frequently with exenatide OW and albiglutide than exenatide BID and liraglutide. Both exenatide formulations and albiglutide may be associated with higher incidences of injection-site reactions than liraglutide and dulaglutide. GLP-1RA use in clinical practice should be customized for individual patients, based on clinical profile and patient preference. Ongoing assessments of novel GLP-1RAs and delivery methods may further expand future treatment options.