Incretins: New Treatments for Type 2 Diabetes

This piece has been adapted from an article written by Alan J. Garber, MD, PhD, FACE.

Incretin [in-KREE-tin] hormones are a new type of treatment for managing people with type 2 diabetes.

Incretin hormones raise insulin after meals, which then lower blood sugar. Incretins also decrease a hormone called glucagon [GLOO-kah-gon], which then raises blood sugar. Incretin hormones play a very important role in keeping the blood sugar in the normal range in people without diabetes. In people with type 2 diabetes, incretin hormones are reduced, and they also slowly lose their ability to make insulin over the years. This is the reason that patients with type 2 diabetes will need insulin someday to control their blood sugar.

Incretin hormones show a lot of promise for long-term benefit. This is because these drugs might slow down insulin loss. And, unlike some older blood sugar medications, incretin hormones have fewer side effects. For example, drugs such as glyburide [GLIGH-bure-ride], glipizide [GLIP-ih-zide], or glimepiride [gly-MEP-ih-ride] that increase blood insulin can cause weight gain and low blood sugar.

GLP-1 is one of the incretin hormones. GLP-1 slows down the emptying of food from the stomach. So, food stays in the stomach longer and this makes people feel full. It also works on the brain to decrease appetite. With less food eaten, it can help people lose weight. But, GLP-1 is destroyed very quickly in the body by an enzyme called DPP-4. In fact, over half of GLP-1 is gone in two minutes! Because of this, GLP-1 itself cannot be used for treatment.

There are two main ways of getting normal incretin hormone action. The first way is to use agents that are very similar to GLP-1, but are not destroyed so rapidly. These drugs come as injections. Exenatide [ex-EN-ah-tide] (Byetta) is one of these drugs and is injected twice daily. Recently, a new human GLP-1 look-alike drug, also injected, has been approved for patients with type 2 diabetes. This new drug called liraglutide [lir-AH-gloo-tide] (Victoza) is injected once a day. These two agents do not cause very low blood sugars unless the person is also taking other drugs that can cause low blood sugar. Liraglutide can be taken any time during the day, but exenetide should be taken before meals. People taking liraglutide lost almost twice as much weight and lowered their blood sugar almost twice as much compared to people taking glimepiride. Liraglutide should not be used in patients with a certain thyroid cancer called medullary [MED-yoo-lerry] cancer of the thyroid or in people with a family history of this kind of cancer. Inflammation of the pancreas (called pancreatitis [pan-kree-ah-TITE-iss]) has been seen in patients treated with either exenetide or liraglutide, although this side-effect has not been proven. The main side effect of both of these drugs is feeling sick to the stomach and throwing up, which usually go away after a few weeks.

The second way to increase blood incretin hormone action is to block the fast destruction of GLP-1. This can be done by blocking the DPP-4 enzyme. Sitagliptin [sit-ah-GLIP-tin] (Januvia) and saxagliptin

[SAX-ah-GLIP-tin] (Onglyza) are two medications that can be taken by mouth. They do not cause low blood sugar, and they work well with other diabetes drugs, such as metformin. However, unlike exenetide and liraglutide, they do not cause loss of appetite or weight loss.

You need to discuss with your health-care team whether you are a good candidate for these new agents. They can help you use them well and safely. The weight loss seen with the injected incretins can be a major benefit to many people with diabetes.

Dr. Alan Garber graduated from Temple University, Philadelphia, in 1968, completed a PhD in Biochemistry in 1971, and a residency in Internal Medicine. Subsequently, he was a fellow in Metabolism and then a junior faculty member at Washington University Medical School and Barnes Hospital in St. Louis. In 1974, he transferred to Baylor College of Medicine in Houston, where he is presently a Professor in the Departments of Medicine, Biochemistry and Molecular Biology, and Molecular and Cellular Biology. Dr. Garber currently serves as Secretary of AACE.