We’re going to go over these four classes:
Sulfonylureas work on the pancreas and try to increase the beta cell production of insulin. This assumes the pancreas is sluggish and it tries to stimulate it. There’s two generations of sulfonylureas. It’s quite rare to see a first generation utilized anymore. The first generations are the older ones. If one fails at a maximum dose, that means all first generation sulfonylureas will fail and a first generation sulfonylurea is not going to work. As for the second generations, if one fails at a maximum dose, you could try the other ones.
First Generation Sulfonylureas
- Chlorpropamide (Diabenese)
- Tolazamide (Tolinase)
- Tolbutamide (Orinase)
Second Generation Sulfonylureas
- Glipizide (Glucotrol)
- Glyburide (DiaBeta, Micronase)
- Glimepiride (Amaryl)
Side effects: Tolbutamide concern is: tinnitus. Chlorpropamide concern is cholestatic jaundice (thick bile or bile plugs in the biliary passages of the liver)
Hypoglycemia: There’s a concern that sulfonylurea’s can cause hypoglycemia, just like insulin would. We have to teach patients about the symptoms of hypoglycemia (racing heart, sweaty, shakiness) to counteract this in case it happens.
Cardiovascular abnormalities: Every drug on this list has a warning for cardiovascular abnormalities. Is it really the drug that causes the abnormalities? Not necessarily. The diabetes itself can cause it. One of the long term consequences of diabetes are the cardiac problems.
Biguanides (Metformin; Glucophage)
This one mechanism of action is different than sulfonylureas. It doesn’t work on the pancreas. It works on the peripheral cells to make them more sensitive to the insulin that’s in the blood stream. A patient may be on both a sulfonylurea and a biguanide. A sulfonylurea may be a Step 1 drug. A biguanide may be a Step 1 or Step 2 drug.
The biguanide is used for a relatively new terminology called a prediabetic. Now we are saying if your blood sugar is between 100-110, you may be considered prediabetic because we want the blood sugar below 100 these days. This drug may prevent a prediabetic from becoming a diabetic.
Renal problems: One of the consequences of diabetes if renal failure. You can’t use this drug if you have any kidney impairment.
Radiologic Dye: If a patient is going to go through a test that requires a radiological dye, this drug must be stopped a few days in advance.
If a person has renal problems or is administered a radiological dye, lactic acidosis may develop.
These increase the sensitivity of the peripheral cells and the hepatic cells to insulin. It doesn’t directly work on the pancreas. This isn’t a step 1 drug. This may be a Step 2 or Step 3 drug. The reason for that is because a thiazolidindione that used to be on the market, had 46 deaths associated with it due to liver failure. The drug manufacturer was guilty for withholding information regarding the importance of performing monthly liver function tests with this drug.
Since then, we’ve found other issues with the other thiazolidindiones on the market such as pioglitazone (Actos) and rosiglitazone (Avandia), so their use is going down in the market real fast. We need liver function tests for these drugs as well but that’s not the problem. We’re seeing an increased risk for cardiac abnormalities. For the rosiglitazone specifically, we’re seeing an increased risk of cancer and it’s become so substantial that no pharmacy can carry it anymore. It must come through a mail-order pharmacy and the doctor must document the reason it is being used.
- Increases sensitivity of peripheral cells and hepatic cells to insulin
- Deaths have been associated with troglitazone – liver failure
- Associated with causing cardiac abnormalities
- Not first line therapy
- Examples: pioglitazone (Actos®), rosiglitazone (Avandia®)
Acarbose would be the third or fourth step drug you’d use and it’s only going to be successful if the patients blood sugar is close to where you want it. It’s only going to lower the blood sugar by maybe 5 points at most. This works differently than anywhere else. It works in the intestinal tract by decreasing the absorption of disaccharides (not monosaccharides). This means it does cause a problem for a diabetic. When a diabetic gets the shakes and palpitations, that means their blood sugar is low and therefore they will have some juice or candy which are usually mostly made of disaccharides. So instead of candy or juice the patients must have a monosaccharide such as glucose or dextrose tablets with them.
- Acarbose (Precose®)
- Decreases oral absorption of disaccharides
- Minimal effects on blood sugar
- 3rd or 4th line agent
- Caution: Cannot reverse hypoglycemia with oral dissacharides