The development of incretins

In 2007, agents known as incretins became available for the treatment of type 2 diabetes in the UK. Sitagliptin, an oral DPP-4 inhibitor, and exenatide, an injectable GLP-1 agonist have become widely used in clinical practice and have been followed on to the market by another three incretin agents. The area continues to develop with the anticipated launch of once-weekly GLP-1 agonist later this year and reports of the efficacy of once-a-month regimens.

The development of incretins has not, however, been a smooth path. Post-licensing reports suggesting a link between exenatide and pancreatitis have lead to all incretins carrying this as a warning, even though the association has not been proved. Taspoglutide (a once-weekly GLP-1 agonist) was recently pulled from clinical development following reports of acute allergic reactions. And only this month, a paper was almost published suggesting a six-fold increase in the risk of pancreatic cancer in patients receiving incretin therapy. I say ‘almost’ because the manuscript which was available on-line for several weeks has now been withdrawn by the journal following major criticism from incretin manufacturers.

What is to be made from these events? Are the newer diabetes agents really more dangerous than the old ones or should we now expect this kind of scare story for all new drugs as competing agenda fight it out in the medical press?

Professor Steve Bain