By: Robert Tanenberg
1. How do these oral hypoglycemic agents (OHAs) work?
The drugs work in three ways:
The sulfonylureas such as Glucotrol (glipizide) and Amaryl (glimepiride) “pump up” the patient’s own beta cells to make more insulin.
The short-acting insulin drugs known as meglitinides (Prandin) and phenylalanine derivatives (Starlix) also stimulate beta cells, but their effect is very short and they must be given just prior to each meal. The biguanides and thiazolidinediones (TZDs) (Glucophage, Actos and Avandia) work to make the liver and muscles more sensitive to the patient’s own insulin. In other words, these drugs reduce insulin resistance, which is the hallmark of type 2 diabetes.
The alpha-glucosidase inhibitors (AGIs) such as Precose and Glyset block absorption of starches from the intestine.
2. What are the benefits of these medications?
In patients with type 2, these drugs will usually lower blood glucose values, help patients achieve better A1C values and reduce the risk of complications from diabetes.
3. What are the side effects of the OHAs?
Some of the medications (Glucophage and Precose) can cause stomach upset or diarrhea. Long-acting formulations of Glucophage (Glucophage XR, or extended release) may limit these problems. Starting with lower doses and gradually increasing the dose will help prevent many of these problems. Fluid retention (edema) is a serious side effect of the TZDs such as Actos and Avandia. This side effect is not overcome with the use of most diuretics (water pills), and often the drug must be stopped when edema is significant.
4. How much will each type of OHA lower my A1C levels?
The sulfonylureas, biguanides and TZD drugs may lower A1C by one or two percentage points. The other drugs usually lower A1C by only 1% or less.
5. Which OHAs are most likely to cause weight gain or weight loss?
Any drug that stimulates insulin release (such as Amaryl) may lead to weight gain, although the short-acting drugs (Prandin) are less likely to cause weight gain. Both Actos and Avandia often lead to weight gain, which is even more likely if they are given with insulin. Only Glucophage (metformin) and the AGIs do not cause weight gain. In some patients, metformin leads to weight loss.
6. Which OHAs cause hypoglycemia?
Any drug that stimulates insulin release (such as Glucotrol) may lead to hypoglycemia, although the short-acting drugs such as Starlix are less likely to cause low blood glucose if taken correctly.
7. Which of these medications can be take only once per day?
Most of the sulfonylureas come in a long-acting formulation. The TZDs are taken once a day. The short-acting insulin stimulators (Prandin and Starlix) and the AGIs (Precose and Glyset) must be taken with each meal and snack.
8. Which OHAs are best for lowering after-meal blood glucose?
Prandin and Starlix and Precose and Glyset reduce post-meal blood glucose values.
9. Do any of the OHAs protect the heart?
Yes. Studies have found that Glucophage and Actos may lower risk for cardiovascular disease in patients with type 2.
10. Which OHAs should be avoided by patients with heart disease?
Patients with a history of congestive heart failure should not take Glucophage or the TZDs (Actos or Avandia). Patients with a history of unstable angina need to avoid becoming hypoglycemic from any insulin stimulators, since low blood glucose may precipitate angina or even a heart attack. Also, patients with known coronary artery disease may have problems with the sulfonylureas, which cause the loss of a heart-defensive mechanism known as ischemic preconditioning.
Note: Any patient who has both diabetes and heart disease of any kind should have a cardiologist review his or her diabetes medications.
11. Is it safe for elderly patients with type 2 to take OHAs?
Maybe. The answer depends on many factors, and it is best to check with an experienced physician if you or an elderly relative is taking one or more of these drugs.
12. Is there a benefit to taking more than one of these medications?
Yes. Most patients who have had type 2 for more than five years need at least two drugs from different groups to achieve an A1C under 7%.
13. How many different OHAs can I take together?
Two or three different oral agents are often prescribed by physicians for patients with type 2. However, most people taking three OHAs will obtain better glycemic control when insulin is added to two drugs when their A1C is above 8%. It is not advisable to take four different OHAs.
14. Are combination pills useful for most patients?
Yes and no. They are more convenient because they reduce the number of pills the patient must take each day. However, these pills are more expensive than the generic agents, and physicians are unable to titrate each drug independently, which is a definite disadvantage.
15. Can OHAs be taken together with insulin?
Yes. It is now the standard of care to continue OHAs when insulin is added either as a single dose (for example, bedtime Lantus) or given in multiple doses. The OHAs most commonly continued with insulin are Glucophage, Actos and Avandia.
See our Type 2 Meds Reference Guide