Steven V. Edelman, MD
TCOYD Newsletter, Vol. 25, 2008

Developments in an Important Class of Treatments for Type 2 Diabetes

Diabetes affects multiple hormones in the body; not just insulin. Incretins are hormones released from the intestines after eating that cause insulin secretion and appetite suppression. Incretins also reduce glucagon levels and normalize stomach motility, both of which are very important ways the body controls blood glucose levels after eating. Remember, glucagon is a hormone that tells the body’s liver to convert glycogen into glucose and release it into the blood stream. Stomach motility is a vital part of digestion. It has to do with how the body moves food through the stomach by muscular contractions.

Incretin Therapy

Throughout the natural history of type 2 diabetes, people stop producing some important incretin hormones. By replacing these hormones, people with type 2 diabetes can achieve both better glucose levels in the morning and after eating, as well as weight loss. This latter effect is very encouraging for thousands of people because several therapies currently used to treat diabetes can lead to increased weight, which is frustrating for everyone!

One of the most well understood incretins in the human body is called GLP-1. However, normal GLP-1 cannot be used as a practical pharmaceutical agent because once administered, enzymes in the body inactivate it within 90 seconds. To counteract this, scientists have figured out a way to trick the body by developing treatments that mimic GLP-1, but are different enough to fool the enzyme that would normally break it down. In this manner, the incretin “mimetic” does all the good things an incretin normally does to improve blood sugar levels and suppress appetite while remaining resistant to enzymatic breakdown. In addition, incretins do not lead to hypoglycemia or low blood sugar levels, which is another key safety feature in this group of therapies. Incretins are classified as peptides and can only be taken by injection since they are destroyed by stomach acids if taken orally (the same reason that insulin must be injected).

First in Class

Byetta (exenatide) became available in the spring of 2006 as the first therapy mimicking the incretin GLP-1. It was developed by both Amylin and Lilly pharmaceutical companies, and was originally discovered in the saliva of the Gila Monster, a poisonous lizard indigenous to Arizona (please see chapter 6 of the book Taking Control Of Your Diabetes, 3rd edition). Currently in development is the once weekly formulation of Byetta, which has all of the benefits of the already available twice-daily Byetta, with even better glucose control and similar weight loss.

Competition in Class

Liraglutide is another incretin mimetic being developed by Novo Nordisk, the makers of Novolog and Levemir insulins. Liraglutide is a once daily formulation and its structure is very similar to human GLP-1 but altered slightly to make it resistant to the enzyme that normally breaks GLP-1 down. It too leads to improved glucose control and weight loss. It should be available in the near future, most likely before the once weekly Byetta formulation. Incretin mimetics represent a novel, safe and very efficacious class of therapies that many diabetes experts, including myself, say will change the landscape of treating type 2 diabetes. As new incretins come to market, both physicians and people with diabetes will have more choices for individualized treatment plans. There is no question that with the further development of incretin mimetics, people with diabetes will gain important tools to better control blood sugar.

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