Glucagon-like peptide-1 receptor agonist (GLP-1RA) treatments were first launched in the United Kingdom in 2007, when exenatide was marketed by Eli Lilly as a twice daily injection (Byetta) for the treatment of patients with type 2 diabetes (T2DM). Since that time, there have been major changes in the way that GLP-1RAs can be administered, with new formulations being developed at a rate not seen with other diabetes therapies.
There are now two once-daily GLP-1RAs available in the UK (Victoza & Lyxumia) and a once weekly (QW) version of exenatide (Bydureon) became available in 2012. The uptake of the QW preparation has been less impressive than one might have expected, reflecting not only the complexity of the injection (the formulation needs to be resuspended before administration) but also the fact that company ownership of the brand has changed several times since it was launched. At least two other once weekly GLP-1RAs will become available over the coming months, probably with simpler injection devices and, one assumes a more coordinated marketing strategy; so, we will see.
Developments with the exenatide molecule, however, continue apace. Glycosmedia recently reported the first non-injectable GLP-1RA from Aegis Therapeutics, a patented exenatide metered nasal spray and Diartis Pharmaceuticals inc. have applied XTEN half-life extension technology to allow for once-monthly dosing of the drug. Meanwhile, Intarcia have trialed the ITCA 650 implantable device, a miniature osmotic pump system that is designed to deliver continuous subcutaneous release of exenatide for up to 12 months following a single placement i.e. a yearly treatment!
Finally, NovoNordisk have a weekly GLP-1RA going through phase 3 clinical trials which appears to be amenable to oral formulation. An early phase clinical trial examining dose range, escalation and efficacy of oral semaglutide in subjects with T2DM began recruitment towards the end of 2013 and should complete this year.
If only all of these advances could be applied to insulin which stubbornly remains a subcutaneous injection …
Professor Steve Bain
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