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The Incretin Saga: Mimetics, Enhancers, and Inhibitors
Illustration of Incretin-based Therapies courtesy www.NDEI.org
A lot of new medicines have come out, with a pile of new acronyms: GLP-1, DPP-4, BYOB…well, that last one is probably familiar, but a little background on the other two might not be out of place. You’re going to be seeing a lot more of them in the future, and it’ll help to be on speaking terms.
First of all, what is an incretin, anyway? An incretin is a hormone released from cells in the gut in response to eating food. Incretins were discovered when scientists noticed that people secreted more insulin after actually eating glucose than after being given a comparable amount of glucose intravenously. They knew there had to be a trigger for that extra insulin secretion, and the trigger was incretin.
Gulp-1, A Gutsy Incretin
The star incretin in diabetes treatment, and our hero in this little tale, is glucagon-like peptide-1, or GLP-1. After a meal, the gut secretes GLP-1 in response to the arrival of food from the stomach. GLP-1 then does several good things to lower blood sugar. It binds to receptors on the pancreatic beta cells and stimulates the release of insulin. It also reduces the secretion of glucagon by the pancreas. (Glucagon causes the liver to convert glycogen to glucose, thereby increasing blood sugar.). In addition, GLP-1 slows down stomach emptying and nutrient absorption. In people without diabetes, this cycle works smoothly. In people with diabetes? Not so much.
In diabetic people, our friendly incretin GLP-1 needs some help. Modern science has come up with two kinds of medicine that increase the action of GLP-1. The first are incretin enhancers, and the second are incretin mimetics.
Gulp Saved From Dip By the Gliptin Sisters
Without artificial help, our hero incretin GLP-1 is a bit of a weakling; it lasts only one or two minutes in the system. That’s because an enzyme called DPP-4 (short for dipeptidyl peptidase 4) very efficiently breaks down GLP-1. In order to make GLP-1 last longer, a medicine is needed to slow down, or inhibit, the enzyme DPP-4. In plain language, we need something to stop Dip the Destroyer from crunching our hero Gulp.
Vildagliptin (Galvus by Novartis, not yet FDA approved) and sitagliptin (Januvia by Merck) are DPP-4 inhibitors. By slowing the action of DPP-4, they delay the breakdown of GLP-1 and thereby enhance its action. Now GLP-1 can stick around longer and carry out all the great blood glucose-lowering actions for which it is so justly famous. It’s easy to remember these two medicines, our DPP-4 inhibitors, as the lovely sisters Vilda and Sita Gliptin, who whip the evil Dip.
Gulp Mime Lasts Longer
The second kind of incretin-increasing medicine is called an incretin mimetic. It’s a medicine that outright copies, or mimics, the action of our hero incretin GLP-1, but is resistant to the evil enzyme DPP-4. As a result, it can carry out its useful job for much longer than poor vulnerable GLP-1, who can’t stand up to DPP-4 for longer than a minute without breaking down. Byetta (exenatide) is an incretin mimetic. It is taken twice daily by injection.
So there you have the story, and now you’ll have a much easier time keeping all the characters straight.
Categories: Blood Glucose, Blood Sugar, Diabetes, Diabetes, Food, Insulin, Type 2 Medications
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Diabetes Health
Diabetes Health is the essential resource for people living with diabetes- both newly diagnosed and experienced as well as the professionals who care for them. We provide balanced expert news and information on living healthfully with diabetes. Each issue includes cutting-edge editorial coverage of new products, research, treatment options, and meaningful lifestyle issues.
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Topics
- Diabetic / Diabetes Health
- Type 1 / 1.5 Diabetes
- Type 2 Diabetes
- Blood Glucose / Sugar
- High/Low Blood Sugar / Fast Acting Glucose
- Insulin- Pumps, Pens & Syringes
- Continuous Glucose Monitors, CGM, Infusion Sets
- Type 2 Medications
- Hyperglycemia
- Hypoglycemia
Comments
Linda von Wartburg's article is very helpful to anyone who wants to keep the "mechanism of action" in mind when using the newer diabetes medications.
I suggest that the diabetes community adopt her memory aids when learning about incretin.
M. Lewis, M.D.
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