With respect to continuing either metformin or glyburide throughout pregnancy for those patients who are treated with these drugs during the preconception stage, the main concern in my opinion is whether the drugs can achieve the levels of glycemic control desired in pregnant women with type 2 diabetes. Because current data have shown that the level of glycemia—and not the drug—is associated with any increased rate of anomalies, I believe patients can remain on these drugs as long as the targeted level of glycemic control is maintained.
Overall, considering that we have a more extensive, more conclusive body of evidence for glyburide than metformin—and considering that glyburide does not cross the placenta—metformin is generally a second choice for me.
Pearls of Management
GDM and type 2 diabetes are essentially the same disease. They are similar in risk factors and in metabolic and endocrine abnormalities. Both are characterized by peripheral insulin resistance, decreased insulin secretion (reflecting declining beta-cell function), and impaired regulation of hepatic glucose.
GDM represents an early stage of the deterioration continuum toward type 2 diabetes. It is characterized by a milder glycemic profile. As I alluded to in a previous Master Class installment (“How Type 2 Diabetes Complicates Pregnancy,” September 2009, p. 28), though, it is increasingly believed that many of the women who are diagnosed with gestational diabetes actually meet the criteria for type 2 diabetes.
Because oral antihyperglycemic agents are the gold standard for therapy in type 2 in the general population—the landmark U.K. Prospective Diabetes Study (UKPDS) of type 2 diabetes showed that 70% of patients achieved desirable levels of glucose control with the use of glyburide—it is sensible to assume that women with GDM or early type 2 diabetes will respond to oral therapy with even greater success.
In general, oral glucose-lowering agents will decrease HbA1c levels by 1%-2% (insulin, by 1%-2.5%). This roughly corresponds to a drop in fasting blood glucose levels of 30-60 mg/dL.
Oral therapy should be initiated when women cannot achieve fasting blood glucose levels of 95 mg/dL or less, or postprandial levels of 120 mg/dL or less after 2 hours. Diet and exercise can be recommended first for many of our patients, of course, but we must do so with careful consideration of the time that we have to meet target levels of control and prevent macrosomia and other adverse outcomes. Research has shown that at least 60% of patients with GDM eventually will require pharmacologic therapy.
Any pharmacologic therapy necessitates frequent dose adjustment to obtain the desired effect of the drug. Oral antihyperglycemic drugs should be increased only to the maximum dose allowed (20 mg daily in the case of glyburide).
The maximal dose of a drug and steady state are different in nonpregnant and pregnant patients, of course, because drug clearance is higher during pregnancy. However, in order to minimize any potential for complications like maternal hypoglycemia, our aim in diabetes management is to provide the minimal dose that will result in a desirable level of glycemic control.
Different oral antihyperglycemic agents act through diverse mechanisms, and the drugs' characteristics provide a physiological approach to the treatment of type 2 diabetes and GDM. Combination therapies will enhance the effect of these drugs on glucose metabolism, and “whole” patient care (including glucose monitoring, education, and diet adherence) will determine overall success in managing this disease and maximizing the quality of perinatal outcomes.
When insulin is added for the patient treated with oral agents, a single dose at bedtime can be sufficient in many cases. One of the benefits of this combination is the need for a lower dose of insulin. Insulin therapy alone should be used when other combinations have failed and is not limited by a maximum dose.
In obstetrics, we've lagged at least 2 decades behind the field of diabetes management in the general population. Now, however, we should be embracing the use of oral antihyperglycemic agents as the standard of care. We may find with further research that other drugs may have a greater therapeutic effect, but for now glyburide is the best front-line choice for glycemic control.
Glyburide Management
1. Start with 2.5 mg in the morning. If needed, drug titration should occur every 3-7 days.
2. Increase the morning dose by 2.5 mg.
3. Add the evening dose of 5 mg.
4. Increase the morning dose by 5 mg to 10 mg.
5. Increase the evening dose by 5 mg to 10 mg.
Note: The maximal dose is 20 mg daily.