Sep 3, 2010

By Trevor Shewfelt, Pharmacist at the Dauphin Clinic Pharmacy

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The information in this article is intended as a helpful guide only. It is not intended to be used as a substitute for professional advice. If you have any questions about your medications and what is right for you see your doctor, pharmacist or other health care professional.

There are some new medications available to treat diabetes. As a group they are called incretins. Lets look at how they work.

First a thumb nail sketch of diabetes. There are two main types of diabetes, Type 1 and Type 2. In Type 1 diabetes, the special cells that make insulin stop. So Type 1 diabetics must inject insulin or they will die. Type 1 diabetics only account for about 20% of the diabetics in Canada. Almost 80% of diabetics out there have type 2 diabetes. In type 2 diabetes, the person is still producing insulin, but the muscle, fat and other cells dont listen to the signal from insulin to suck up glucose from the blood stream. We call that insulin resistance. Let me tell you a fairy tale about a locksmith.

You eat some food and your gut breaks it down into all its useful parts. One of the parts is glucose. Glucose is fuel for the body. The glucose goes into the blood stream which takes it all over the body. You have a little locksmith in your pancreas making keys. These keys are insulin. The keys also float through the body in the blood stream. When the keys get to a location like a muscle cell, they open a door in the cell which lets the glucose in. The glucose fuel is then used so the muscle can move.

In type 2 diabetes we have a problem with insulin resistance. In our little fairy tale that means the locks on the glucose doors get rusty. Even if there are insulin keys floating around, the insulin key cant open the glucose door. So in type 2 diabetes, we give the patient medications. We can give them insulin which gives us more insulin keys to force the rusty locks open. We can give them sulfonyureas like glyburide. Glyburide whips the locksmith into making more insulin keys. That works, but we worry about eventually whipping the locksmith so much he quits. We can give the patient drugs like metformin, rosiglitazone (avandia), or pioglitazone (actos). These drugs do several things, but they basically spray some WD-40 onto the glucose locks so the insulin keys can work better. They seem to reduce insulin resistance.

The biggest problem with type 2 diabetes is we dont seem to be winning the war. Type 2 diabetes is becoming more common. The increase is blamed, at least in part, on the fact we are getting less active, eating more poorly and getting more obese. Type 2 diabetes leads to the big four: blindness, heart disease, kidney disease and amputation. And even in the patients we are treating now, it seems like their blood sugars keep going up despite the fact we are using multiple medications and insulin on them. It sure would be nice if we had a new tool in the tool box.

Well, the new tools are called incretins. In our little locksmith fairy tale, incretins give the locksmith lots of praise instead of whipping him, so he lives longer and makes more insulin keys. The incretins also reduce glucagon. Glucagon opens doors in cells that release glucose from the cells. That is the exact opposite of insulin. So too much glucagons makes it harder for insulin to do its work and contributes to insulin resistance.

Now to leave our little fair tale and talk a little science. Incretins are hormones made in your gut, and are released when you eat glucose containing foods. The naturally occurring incretins have names like Glucagon Like Peptide 1 (GLP-1), Glucose-dependent Insulinotropic peptide and gastric inhibitory peptide. GLP-1 does some interesting things. It delays the emptying of the stomach, it makes beta cells produce more insulin, reduces glucagon secretion and convinces your brain that you are less hungry.

Scientists found if GLP-1 was injected into patients it reduced blood sugar levels, had a low risk of making the blood sugar go too low, caused weigh loss, helped the insulin making cells stay healthy, but causes some nausea and vomiting. That was good, but the injected GLP-1 was broken down by the body within minutes. To get any good effects they had to continuously pump it into the test subjects. That would not be practical for the average type 2 diabetic.

So the drug companies have developed two different types of GLP-1 like products. The first type of incretin is called DDP-4s and they block the enzyme that breaks down the GLP-1. This makes the GLP-1 in the body last longer. They are oral pills and have names like Januvia (sitagliptin), and Onglyza (saxagliptin). The second type of incretin is called a GLP-1 analog, because they act like GLP-1 in the body, but they arent broken down as fast. The first on available in Canada is called Victoza or liraglutide. It needs to be injected.

The incretins you swallow are a little less potent at reducing blood sugar. The pill incretins like sitagliptin and saxagliptin also dont cause nausea like the injections do. They are most appropriate in more mild type 2 diabetes. The incretin you inject once daily called liraglutide will help a patient lose weight, and will lower their blood sugar more. It is likely to cause nausea for the first few weeks and then that should go away. All the new incretins are expensive compared to older medications like glyburide and metformin and none of them have pharmacare coverage yet.

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As always if you have any questions or concerns about these products, ask your pharmacist.


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