Glyburide

So the last time you were at your doctor's office, they told you that you have diabetes and started you on metformin.  You went home and started taking it, and tried to improve your diet and exercise.  Now you are back in the clinic for your first lab tests.  The doctor checks your A1c and it is still not to where it needs to be (less than 7% is the goal).  So what do we do?  Since so many problems can come from diabetes that is not under control, your doctor is going to want to start you on another medication quickly to bring your numbers down faster.

Which medication will they choose?  The American Diabetes Association, as well as other medical organizations, have come up with a "roadmap" of how to treat diabetes using medication.  From my blog last week on diabetes, you know that metformin, combined with lifestyle changes in diet and exercise, is our starting point on the journey.  If your A1c is not low enough at the next visit, doctors have three main options: insulin, sulfonylureas, or TZDs.  If you need a refresher on these categories, or if you are tuning into my blogs for the first time, please read my blog on the different classes of diabetes medications here.

Each option has its own pros and cons, but I'm going to start with the sulfonylureas, since they are the least expensive and most common options, second to metformin.  The first sulfonylurea I'll be covering is glyburide, which also goes by brand names DiaBeta, Micronase, and Glynase.

How does it lower blood sugar: Glyburide helps your body release insulin into the blood.  Remember, insulin is the hormone in your body that helps take the sugar out of your blood and puts it into your cells.  So glyburide puts the insulin where it needs to be - in the blood where your sugars are.  In a very small way, glyburide also makes your cells more sensitive to insulin ("opening the door of the cell" for sugar to enter), but this is not the most consistent way that glyburide works.  Unfortunately, as type 2 diabetes progresses, the body sometimes can no longer make its own insulin.  At that point, glyburide is no longer effective because there is no more insulin there to "move."  But in newly diagnosed type 2 diabetics, glyburide can be very effective.

The effect on your numbers: Like metformin, glyburide also lowers your A1c by about 1 - 2% (a patient with an A1c of 9 could go down to an A1c of 8 or 7 when on glyburide).  Glyburide really doesn't seem to lower a patient's cholesterol levels, which was a benefit that we saw with metformin.

Dosing: Glyburide is usually taken once daily, in doses from 2.5 to 20 mg.  Usually patients are started at 2.5 or 5 mg daily and then increased as needed.  Just like with metformin, your doctor can change your dose every 1-2 weeks if needed.  Glyburide should always be taken with the first meal of the day (within about 30 minutes before).  It is important to always take glyburide with food because otherwise the medication will cause your blood sugar to drop too low (hypoglycemia).  So it's important to state again, always take glyburide with food.

Side effects: Hypoglycemia (dangerously low blood sugar) is one of the most dangerous side effects.  Weight gain can also be a possibility with glyburide (obviously not ideal in most diabetics).  Glyburide is the medication in this class with the most likelihood of these side effects, since it takes the longest to leave your body once it is in there.  The other side effects you might have from glyburide are a feeling of stomach fullness (as if you've just finished eating a big meal), heartburn, rashes/itching, and nausea.  Very rarely, glyburide can cause liver problems (hepatitis).

Who should not take glyburide: Any patients with a "sulfa" allergy should not take glyburide, or any other sulfonylureas (which I will be covering in the next few weeks), because they contain the thing that you are allergic to.  Because of the risk of low blood sugar if not taken correctly, anyone that has a very inconsistent diet or has a history of low blood sugar episodes might not be an ideal candidate for this medicine.  Glyburide should not be used in any patient that is pregnant or breastfeeding.  Also, if you have severe liver or kidney problems, your doctor will avoid using this class of medications.

Drug interactions: The most important thing that I want to stress here is that alcohol must be avoided when taking glyburide.  A simplified way to look at it is that glyburide causes your body to not tolerate alcohol.  You could experience side effects such as nausea, flushing of the skin, vomiting, shortness of breath, and very low blood pressure.   But the most important thing that happens is that it can increase the effect of low blood sugar, which can be very dangerous.  Other medications that can interact with glyburide and make it work better or worse are certain blood pressure medications, diuretics ("water pills"), blood thinners, salicylates (like aspirin), and certain antidepressants.  Remember, check with your local pharmacist or doctor before starting any new medications, both prescription and over-the-counter.  And make sure your pharmacy is aware of all medications that you take so that your pharmacist can check for drug interactions when you come in with a prescription.

Monitoring: Just like with metformin, your doctor is going to monitor your A1c, and you will need to monitor your blood sugar levels daily.  Because of the chance of low blood sugars with this medication, you need to be even more consistent with monitoring your blood sugars, and watching if they are too low.  Signs of low blood sugar include feeling like your heart is racing, headache, confusion, increased sweating, hunger, shakiness, tingling in the mouth, and a feeling of anxiety.

If you start to experience any of these, or if you just don't "feel quite right," check your blood sugar immediately.  You will need to have a snack available right away to eat that contains at least 15 grams of carbohydrates, in order to raise your blood sugar to a safe level immediately.  A list of these types of snacks, as well as other information about hypoglycemia can be found here.  I've copied the list over for your reference, to make it easier:

• 4 oz (1/2 cup) of juice or regular soda
• 2 tablespoons of raisins
• 4 or 5 saltine crackers
• 4 teaspoons of sugar
• 1 tablespoon of honey or corn syrup

Choose what will work for you.  Read labels and find something that is appropriate for your  lifestyle.  It needs to be something that is readily accessible by anyone, especially if you are not feeling well enough to get to it.  Remember, regular soda is needed here, not diet.  When we are trying to raise blood sugar quickly, we need to have sugar, not something that is "diabetes friendly."

Once you've had your 15 grams of carbs, you still need to eat a meal containing complex carbs that will help your body get back up to a normal level.  The foods I just mentioned are simple carbohydrates - your body processes them quickly, your blood sugars rise quickly, and then they are gone.  Complex carbs are things like vegetables, brown rice, whole grain breads, and wheat pasta.  Don't stop with just the 15 gram snack or you might be in the same low blood sugar situation within a few hours.

Place in therapy for diabetes: Glyburide is considered one of the first or second choices for treating type 2 diabetics (second usually to metformin).  This is because it is inexpensive, not a shot like insulin is, and only has to be taken once or twice a day.  It is important to mention that some patients just don't see any results with glyburide, or the other medications in this class, so we try it and then have to switch to something else.  As diabetes progresses and your body changes, sometimes glyburide (and any of the other diabetes medications taken by mouth) does not work as well.  About 5-10% of diabetics every year have this happen.  If it does, we can sometimes switch you to another medication within the same class.  Next week I will be talking about another one within this class, so don't miss it!

In case you are curious and want to know more about glyburide, you can find more information here.

If this turns out to not be the right drug for you, don't worry.  As you will see, we have plenty of options.  And as Phil has talked about, you do not have to be a "victim" of diabetes.  You can make changes in your own life that will help to fight back the disease.  They won't cure it, but they will make our medications much more effective, and will keep you living the healthy and happy life that you deserve.  I'm thinking about you, each and every one of you, and wishing you all the best in your fight!  Keep up the good work!

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As a disclaimer, I am your "virtual" pharmacist, here to provide you with information and answers to questions.  However, I am not your local pharmacist and could, in no way, be aware of your specific medical needs.  Remember to always check with your medical provider and pharmacist before stopping or starting any new medications.  My posts are based on general pharmacy principles and should not considered as your "first opinion" when it comes to your health.  Please consult with your doctor and pharmacist about anything regarding your health.

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