NON-INSULIN DRUGS TO LOWER BLOOD GLUCOSE

Over the past few years more and more medications have become available to help control blood glucose.

I discuss insulin options here.
 
On this page I first list the available classes of non-insulin medications, their main pros and cons, then I discuss the approach to selecting the "best" medicine:
 

Sulfonylureas

These drugs work by stimulating the pancreas to make insulin.
 
Here's what's good about sulfonylureas:

  • They are very effective at bringing down elevated blood glucose levels.
  • They're inexpensive.
Here's what's bad about sulfonylureas:
  • They lose their effectiveness faster than most other classes of blood-glucose lowering medicine. Therefore, within a few years of taking this type of medicine it won't be of much benefit to you.
  • They tend to cause weight gain.
  • They not uncommonly cause episodes of hypoglycemia. (This is especially true of glyburide, hence glyburide is, for most people, not as good a sulfonylurea to use as the other types.)
These are the most commonly used types of sulfonylureas:
  • Gliclazide
  • Glimepiride
  • Glyburide (also known as glibenclamide)


Metformin

Metformin isn't actually the name of the class - the class is called biguanides - but since metformin is the only drug in the class I'm taking a small liberty here.

Metformin works primarily by reducing how much glucose the liver releases.
 
Here's what's good about metformin:

  • It is quite effective at bringing down elevated blood glucose levels.
  • It does not cause weight gain.
  • There is some evidence that it may reduce the risk of heart attack (or maybe even some types of cancer).
  • For women with certain types of infertility (particularly PCOS), it may improve fertility.
  • It's inexpensive
Here's what's bad about metformin:
  • It can cause nausea, abdominal cramps, and diarrhea. (This, however, is not usually a problem if the dose is started low and only slowly increased.).
  • It should not be used if you have advanced kidney failure. 
Metformin is considered the best initial medication to treat type 2 diabetes in almost all cases. (The one most significant exception being if your blood gluocse is extraordinarily elevated in which case you should be immediately placed on insulin.)


Glinides

These drugs work by stimulating the pancreas to make insulin.
 
Here's what's good about glinides:

  • They are reasonably effective at bringing down elevated blood glucose levels.
Here's what's bad about glinides:
  • They are not as powerful as many other medications.
  • They need to be taken before each meal.
  • They can cause hypoglycemia.
These are the two available glinides:
  • Repaglinide (GlucoNorm)
  • Nateglinide (Starlix)

Alpha-glucosidase Inhibitors

These drugs work by slowing down absorption of glucose from the intestine.
 
Here's what's good about alpha-glucosidase inhibitors:

  • They don't cause hypoglycemia.
  • They are very safe with serious side-effects being almost unheard of.
Here's what's bad about alpha-glucosidase inhibitors:
  • They tend to cause lots of flatulence. (Less of a problem if started in a low dose and only gradually increased.)
  • They are not very potent at lowering blood glucose levels.
The most commonly used alpha-glucosidease inhibitor is acarbose (GlucoBay).


Thiazolidinediones (TZDs)

These drugs work primarily by increasing the amount of glucose taken up by muscle and fat cells.
 
Here's what's good about TZDs:

  • They are quite effective at bringing down elevated blood glucose levels.
  • They tend not to lose their effectiveness as quickly as most other medications used to lower blood glucose.
Here's what's bad about TZDs:
  • They cause weight gain.
  • They increase the risk of heart failure.
  • They increase the risk of osteoporosis.
  • Depending on the particular TZD, they may adversely affect your cholesterol levels.
These are the two available TZDs:
  • Pioglitazone
  • Rosiglitazone
Because of the risk of adverse effects of TZDs - and in particular, the perceived risks of rosiglitazone - TZDs are being used less and less often.


DPP-4 Inhibitors

These drugs work by stimulating the pancreas to make insulin and reducing how much glucose the liver releases.
 
Here's what's good about DPP-4 inhibitors:

  • Data available so far suggests these drugs seldom have adverse effects and are remarkably safe.
  • They do not cause weight gain.
  • They do not cause hypoglycemia.
Here's what's bad about DPP-4 inhibitors:
  • They are not as potent as a number of other available drugs
These are the available DPP-4 inhibitors:
  • Saxagliptin (Onglyza)
  • Sitaliptin (Januvia)
  • Vildagliptin (this one is not available in Canada)


GLP-1 Analogues

These drugs work by stimulating the pancreas to make insulin, reducing how much glucose the liver makes, slowing down how quickly the stomach empties food into the intestine, and by reducing appetite.
 
Here's what's good about GLP-1 analogues:

  • They are very effective at reducing blood glucose levels.
  • They lead to weight loss in most people.
Here's what's bad about GLP-1 analogues:
  • They often cause nausea and vomiting. (But this tends to go away within a few weeks if you can put up with it until then.)
  • They are expensive (up to $300 per month in Canada).
  • They are given by injection.
These are the available GLP-1 analogues:
  • Liraglutide (Victoza)
  • Exenatide (Byetta) - this is not available in Canada

Another type of drug called pramlintide (Symlin) is available in some countries, but not in Canada. It is given by injection and is used in certain people with diabetes who are also taking insulin therapy.


Selecting The "Best" Medicine To Lower Your Blood Glucose

What is the "best" medicine to lower your blood glucose? Heck, beats me. Why? Well, because there is no "best" medicine. What is best for you may be entirely different from what's best for your neighbour or your cousin or...

Basically, you, in parnership with your health care team, need to look at your specific situation and make a collective decisiion as to what the best choice is for you as an individual. Having said that, there are guidelines written by diabetes associations to help health care providers in their decision-making. These guidelines are typically distilled down to an algorithm, or series of steps which can be followed. The Canadian Diabetes Association algorithm appropriately obliges health care providers to look at the characteristics of each particular class of drug when making decisions, rather than being a "thou shalt do this" approach. Here is the CDA algorithm:
 

 


As you can see, lifestyle therapy is in the forefront of therapy.

For most people with newly diagnosed type 2 diabetes who require blood glucose-lowering medication, metformin is the best initial choice. Insulin, however, is preferred if your blood glucose levels are exceptionally high; especially if you are unwell from your high blood glucose.

If despite lifestyle and metformin therapy your blood glucose levels are still above target, then you will need additional blood glucose-lowering medication. The various choices are listed in the preceding algorithm (except for GLP-1 analogue therapy as this was not yet available in Canada when the table was designed) with some of their main advantages and disadvantages.              

If after a few months your blood glucose readings are still above target then you will need additional medication.      

One of the single greatest shortcomings in treating elevated blood glucose in people living with type 2 diabetes is undue delay in adding aditional blood glucose-lowering medications. You and your health care team should be striving for you to achieve target blood glucose control within 6 to 12 months of your diagnosis.