Background:  

In vitro and invivo data suggest that glyburide minimally crosses the placenta. A randomized control trial of 404 women with gestational diabetes (Langer, NEJM 343:1134, 2000) suggests that Glyburide could maintain similar blood sugars, Hgb A1C levels, birth weights and macrosomia rates in patients with gestational diabetes when compared with  insulin.  In this NEJM study, there was a 4% failure rate of therapy requiring a switch to insulin.  Given these results and widening clinical experience, it is reasonable to offer treatment with glyburide to pregnant women with glucose intolerance under some conditions.

 

Candidates for Use:  

-Singleton IUP             

-Gestational diabetes - 2 abnormal values, unmodified O'Sullivan's (105, 190, 165, 145)     

-Any gestational age over 10-12 weeks with new diabetes diagnosis.  (This is to avoid hyperglycemia during organogenesis. Attempting use of an oral agent might delay definitive Rx with insulin.)

-Type 2 patient conceiving on an oral agent, well-controlled, may switch       to glyburide.                            .

 

- Multiple gestations (due to growth concerns). 

- Previous poor pregnancy outcome (IUGR, IUFD, macrosomia, birth trauma . . .) - A fasting blood sugar >140, 2 hr post prandial >200.  Hgb A1C >7.

 

All patients should be counseled regarding ADA diet.

All patients should monitor FBS and 3 two hour pp sugars daily. 

·  Offer insulin therapy as the best studied option. 

·  If the patient prefers oral therapy, then  prescribe glyburide 2.5 mg po q AM, increase by 2.5 mg after week one if the fasting blood is >60-90 or a 2 hr post prandial blood sugar is >120.

·  Second week, increase dose by 5 mg weekly up to a total of 20 mg to achieve glycemic control.

 

Treatment Failure:    

Move to insulin therapy.

Defined as: 

-FBS >100 or 2 hr post prandial >120 on 20 mg of glyburide

-or at any time after glyburide initiation with a FBS >120  or a 2 hr post prandial

>180.

 

Insulin drip when needed as standard of care to maintain euglycemia.

 

 

Metformin: 

Pilot data suggests metformin may decrease the spontaneous abortion rate in PCOS patients.  It should only be used after extensive counseling for this indication.  Older data shows a 50% failure rate for metformin when used to treat gestational diabetes.  Metformin is a small molecule that may cross the placenta.  In a South African study, patients were switched to insulin two weeks prior to deliver to avoid neonatal hypoglycemia.  A retrospective cohort from Denmark, (Hellmuth  Diabet Med 17:507, 2000) suggests a higher perinatal mortality rate and increased prevalence of preeclampsia in women on metformin.

 

The data for first generation oral agents was concerning for inadequate blood sugar control and prolonged neonatal hypoglycemia in women with gestational diabetes and these agents should not be used.  Another second generation oral agent, Glipizide, Glucotrol^®, crossed the placenta in in vitro studies. Hence it also has the potential for neonatal hypoglycemia.