Incretins; a non-insulin therapeutic for diabetes mellitus

The American Animal Hospital Association (AAHA) updated their diabetes mellitus guidelines in January this year. A small interesting section of note was their inclusion of incretins under ‘Non-Insulin Therapeutic Agents’. They note that they can be used as an adjunctive to glargine to help achieve remission in cats and to aid diabetic control in dogs.

A couple of years ago I read an article in the Journal of Feline Medicine and Surgery (JFMS) about the potential of Glucagon-like peptide-1 analogs, a type of incretin, as a new approach in the management of feline diabetes. The AAHA guidelines are the first time I have seen them mentioned as a viable adjunctive therapy; albeit with the caveat that more research and evidence into this area is welcome.

This is exciting as it is another avenue for treatment that could help reduce physical burden on owners. It has been shown to increase remission rates in diabetic cats but there is evidence in people with type-2 diabetes that control can be achieved with once weekly injections, and there is potential for monthly injections in the future. These drugs are starting to replace insulin as a safer and longer acting alternative in human medicine.

The primary incretin that is used is Glucagon-like peptide-1 (GLP-1). This compound is secreted from the intestine in response to food. It acts to delay gastric emptying, increase satiety, suppress glucagon secretion and ultimately promotes insulin secretion and improves beta cell function. It’s action is glucose dependant which means it is most active during periods of hyperglycaemia. Due to this mechanism they are safe in euglycemic patients as there is less risk of hypoglycaemia.

The two GLP-1s mentioned in the guidelines are exenatide extended release (Bydureon) in cats and in dogs liraglutide (Victoza). In people exenatide has been shown to be as effective as glargine but safer with fewer side effects and periods of severe hypoglycaemia have been rarely reported. There are other GLP-1s that have potential with longer half-life’s such as albiglutide and dulaglutide but they have not been studied yet in cats.


Papers:

  1. Behrend, E., Holford, A., Lathan, P., Rucinsky, R. and Schulman, R. (2018). 2018 AAHA Diabetes Management Guidelines for Dogs and Cats. Journal of the American Animal Hospital Association, 54(1), pp.1-21.
  2. Gilor, C.; Rudinsky, A.J.; Hall, M.J. New approaches to feline diabetes mellitus: Glucagon-like peptide-1 analogs. J. Feline Med. Surg.2016, 18, 733–743.