Antidiabetic Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
One report describing the use of glimepiride during human pregnancy has been located. Insulin is the treatment of choice for pregnant diabetic patients because, in general, other hypoglycemic agents do not provide adequate glycemic control. Moreover, insulin, unlike most oral agents, does not cross the placenta to the fetus, thus eliminating the additional concern that the drug therapy itself will adversely affect the fetus. Carefully prescribed insulin therapy provides better control of the mother’s glucose, thereby preventing the fetal and neonatal complications that occur with this disease. High maternal glucose levels, as may occur in diabetes mellitus, are closely associated with a number of maternal and fetal adverse effects, including fetal structural anomalies if the hyperglycemia occurs early in gestation. To prevent this toxicity, the American College of Obstetricians and Gynecologists recommends that insulin be used for types 1 and 2 diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (1,2).
FETAL RISK SUMMARY
Glimepiride is a second-generation sulfonylurea in the same class as glipizide and glyburide (see also Glipizide and Glyburide). It is used as an adjunct to diet and exercise, either alone or in combination with other oral agents, in the treatment of type 2 diabetes (non-insulin-dependent diabetes mellitus). It has also been used in combination with insulin when diet, exercise, and an oral hypoglycemic have not controlled hyperglycemia.
Reproduction studies in animals have been conducted with glimepiride. No teratogenic effects were observed in rats and rabbits given doses up to approximately 4000 and 60 times, respectively, the maximum recommended human dose based on BSA (MRHD). However, in some studies, rat pups, nursing from mothers given high doses of glimepiride during pregnancy and lactation, developed skeletal deformities consisting of shortening, thickening, and bending of the humerus during the postnatal period. Moreover, fetotoxicity (intrauterine death) occurred in both rats and rabbits at 50 and 0.1 times, respectively, the MRHD. The fetotoxicity, which has also been observed with other sulfonylureas, occurred only at doses that produced maternal hypoglycemia and was thought to be due to that effect. No effect on the fertility of male and female rats was noted at doses up to 4000 times the MRHD (3).
It is not known if glimepiride crosses the placenta, but the molecular weight (about 491) is low enough that transfer to the fetus should be expected. Hypoglycemia in the newborn may occur if glimepiride is taken close to delivery.
A 2005 case report described the pregnancy outcome of a 33-year-old woman treated with glimepiride for type 2 diabetes mellitus in the first 8 weeks of an unplanned pregnancy (4). Other diseases in the patient were hypertension, hypercholesterolemia, and morbid obesity that were treated with orlistat, ramipril, thiocolchicoside (a muscle relaxant), simvastatin, metformin, ciprofloxacin, and aspirin. When pregnancy was diagnosed at 8 weeks, all medications were stopped, and she was started on methyldopa and insulin. She gave birth at 38 weeks to a 3.470-kg female infant with Apgar scores of 5 and 7 at 1 and 5 minutes, respectively. No minor or major malformations were observed in the infant (4).
BREASTFEEDING SUMMARY
No reports describing the use of glimepiride during human lactation have been located. The relatively low molecular weight (about 491) suggests that the drug will be excreted into breast milk. Because neonatal hypoglycemia is a potential effect, women taking glimepiride should consider changing to insulin therapy while nursing.
References
1.American College of Obstetricians and Gynecologists. Pregestational diabetes mellitus. ACOG Practice Bulletin. No. 60. March 2005. Obstet Gynecol 2005;105:675–85.
2.American College of Obstetricians and Gynecologists. Gestational diabetes. ACOG Practice Bulletin. No. 30. September 2001. Obstet Gynecol 2001;98:525–38.
3.Product information. Amaryl. Hoechst Marion Roussel, 2000.
4.Kalyoncu NI, Yaris F, Kadioglu M, Kesim M, Ulku C, Yaris E, Unsal M, Dikici M. Pregnancy outcome following exposure to orlistat, ramipril, glimepiride in a woman with metabolic syndrome. Saudi Med J 2005;26:497–9.