Sunday, September 2, 2012

Let's Start at the Very Beginning: Classes of T2 Diabetes Medications

For my first post, I'm going to give a brief overview of the various classes of medications used to treat type 2 diabetes.  Within our bodies, blood sugar levels are controlled by various mechanisms.  This is a good thing, because it allows us to "attack" diabetes from various angles. 

For any of you footbal fans out there, you could compare this to what your favorite coach does.  In order to gain yards and score touchdowns, do they always use the same plays for every team they encounter?  Of course not!  Some plays are more effective against different defensive lines, and all circumstances can change from one snap of the football to the next.

This is the same when it comes to treating diabetes.  Every person is unique and has their own body chemistry.  This is the same reason why an allergy medication might work well for one person, but not another.  Pharmaceutical scientists have studied these differences and have developed a wide variety of drugs to treat the causes of high blood sugar (glucose) at every stage.  In future posts I will breakdown each of the currently available type 2 diabetes medications and give you the "need to know" information.  But for now, let's start with the basics.

Biguanides

Don't let this name intimidate you.  Biguanides, like most other classes of medications, are simply named for the molecule that is part of their chemical structure.  In fact, to make things even simpler for you, the biguanide "class" of medications only contains one diabetic medication.  One!  Metformin, a drug that most type 2 diabetics are very familiar with, is the only biguanide currently available in the US that is used for diabetes. 

Biguanides use a few methods for lowering blood glucose levels.  The first method is by making the cells of your body more sensitive to insulin.  If you are unfamiliar with it, insulin is the hormone made by your pancreas that is responsible for "pushing" glucose into your cells.  More glucose in your liver, muscle, and fat tissue = less glucose floating around in the blood.  Too much glucose in your blood, and not in your cells, is what causes diabetes.  In type 2 diabetics, the body starts to not respond to insulin as well as it should, so metformin helps the cells "recognize" insulin again.

The other way that metformin lowers blood glucose levels is by decreasing the amount of glucose produced by the body.  One of my pharmacy professors liked to use the phrase "the liver is a giver."  Your liver is responsible for a wide variety of functions, among which is production of glucose.  During times of fasting or starvation, the liver does this to prevent dangerous drops in blood glucose.  But in diabetics, the extra glucose is not necessary, so metformin stops this.

Another exciting thing about metformin is its ability to produce small decreases in cholesterol.  This is something that I will discuss in future posts.  As you will see, this is uncommon and part of the reason why metformin is the go-to medication for new diabetics.

Sulfonylureas

Another long name based on a chemical structure.  Glyburide, glipizide, and glimepiride are the most well-known students in this class.  Compared to the two different mechanisms of action of the biguanides, sulfonylureas do not provide as much "bang for the buck."  Their main action comes from the ability to stimulate the pancreas to release more insulin.  This causes glucose to enter the cells, decreasing the amount of glucose in the blood. 

Meglitinides

This is a category of medications that we see used much less commonly than the two previously mentioned.  The two meds in this group are Prandin and Starlix, which are currently only available in their brand name form.  Meglitinides are essentially the same as sulfonylureas, except they don't contain a sulfa molecule.  This is important for our patients with sulfa allergies.  They work the same way as the sulfonylureas (increasing insulin release from the pancreas).

Thiazolidinediones

Sometimes you wonder if we are making these names up, don't you?  It's pretty obvious why we abbreviate this class to the term "TZD".  The two current TZDs available in the US are Avandia and Actos.  The main effect of these medications comes from the ability to sensitize the muscles, liver, and fat tissue to insulin.  This allows more glucose to enter the cells and leave the blood stream.  They also show some effectiveness in decreasing the amount of glucose that is released by the liver.

Alpha-Glucosidase Inhibitors

This is a newer class of medications that contains the drugs Precose and Glyset.  Maybe this shows my "nerdy" side a bit, but I find the mechanism of this class to be quite exciting.  Alpha-glucosidase inhibitors work in the small intestine by delaying and preventing complex carbohydrates from being absorbed from what you eat.  This means that the carbohydrates don't enter the bloodstream, and your after-meal (postprandial) glucose readings are much lower.

DPP-4 Inhibitors

Januvia, Onglyza, and Trajenta are the current US available medications in this category.  These medications cause insulin to be produced and released by the pancreas as blood glucose levels rise.  They also decrease the production of glucagon, a hormone that causes the body to break down glucose storage units and dump glucose back into the blood when blood glucose is too low (during periods of fasting or between meals).  Finally, DPP-4 inhibitors improve the function of beta cells in the pancreas, which allows them to better produce the insulin that is needed to keep blood glucose levels at normal levels.

Insulin

Most people are familiar with the use of insulin in type 1 diabetics.  They require insulin because their bodies are no longer able to produce it.  However, insulin is also used as a very effective treatment in type 2 diabetics when oral medications and lifestyle changes are not effective enough at lowering blood glucose. 

I have already discussed insulin a bit within the other drug categories, but let's cover it as its own category, to be thorough.  At low levels, insulin causes the liver to stop producing glucose.  As you increase the insulin dose, that causes the muscles in your body to start taking glucose out of the blood.

Insulin is categorized based on how fast it starts working in the body, and for how long it works (rapid, intermediate, or long acting).  In a future post I will discuss the different types of insulins and injection regimens, but for now this is a good place to start.

Incretin Mimetics

The injectible drugs Byetta and Victoza are the two drugs currently within this category.  These medications work to lower blood glucose by increasing insulin production in response to high blood glucose levels.  They also are unique because they stop glucagon (mentioned earlier) from being released after you eat. 

Other ways that incretin mimetics work to lower blood glucose are by improving the function of beta cells in the pancreas (responsible for making insulin) and causing a feeling of fullness (making the patient eat less and lose weight).

Amylin Analogs

Currently the injectible drug Symlin is the only amylin analog.  Amylin is a hormone that is released by the body, with insulin, to control glucose levels after you eat.  In diabetics, amylin levels are too low.  Symlin acts like amylin in the body; it causes glucose to be absorbed into the body more slowly from the food you eat and also makes you feel fuller faster, leading to less calories eaten and more weight loss.


---So there we have it, a basic overview of the many classes of medications available for treating type 2 diabetes.  In my next series of posts, I will discuss each medication individually, and give you the most important "need to know" information.  As a reminder, every diabetic is different.  I will continue to present information in a general format, but always consult with your personal physician and pharmacist before making any changes in your medications.  I invite you to feel free to ask me any questions you might have regarding diabetes and medications.  Eventually we might have a section of "frequently asked pharmacy questions" in which I answer your questions or address things that I've read about or been asked within my practice recently.  I'm here for you, as a part of your virtual care "team."  Feel free to help me customize my posts to help your needs. 

Dr. K, PharmD


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