Antidiabetic Agent
PREGNANCY RECOMMENDATION: Limited Human Data—Animal Data Suggest Low Risk
BREASTFEEDING RECOMMENDATION: No Human Data—Probably Compatible
PREGNANCY SUMMARY
Less than 2% of acarbose is absorbed systemically, but several metabolites are absorbed in much greater proportions, and the embryo or fetal risk from any of these is unknown. Acarbose is normally used in combination with oral hypoglycemic agents, and these hypoglycemic drugs might not be indicated for the pregnant diabetic. Carefully prescribed insulin therapy will provide better control of the mother’s blood 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 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 type 1 and type 2 diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (1,2).
FETAL RISK SUMMARY
Acarbose is an oral α-glucosidase inhibitor that delays the digestion of ingested carbohydrates within the gastrointestinal tract, thereby reducing the rise in blood glucose after meals. It is used in the management of non–insulin-dependent diabetes mellitus (type 2). Less than 2% of a dose is absorbed as active drug in adults, but the systemic absorption of metabolites is much higher (approximately 34% of the dose) (3).
Reproductive studies in rats found no evidence of impaired fertility or reproductive performance. Doses of acarbose up to 9 and 32 times the human dose (HD) in pregnant rats and rabbits, respectively, were not teratogenic in either species or, at 10 times the HD, embryotoxic in rabbits (3).
A 1998 noninterventional observational cohort study described the outcomes of pregnancies in women who had been prescribed 1 or more of 34 newly marketed drugs by general practitioners in England (4). Data were obtained by questionnaires sent to the prescribing physicians 1 month after the expected or possible date of delivery. In 831 (78%) of the pregnancies, a newly marketed drug was thought to have been taken during the 1st trimester with birth defects noted in 14 (2.5%) singleton births of the 557 newborns (10 sets of twins). In addition, two birth defects were observed in aborted fetuses. However, few of the aborted fetuses were examined. Acarbose was taken during the 1st trimester in five pregnancies. The outcomes of these pregnancies included two spontaneous abortions and three normal newborns (one premature) (4).
A 2002 abstract reported the pregnancy outcomes (birth weight and gestational age at delivery) of 91 women at ≥20 weeks’ gestation who were treated with either acarbose (N = 45) or insulin (N = 46) for gestational diabetes mellitus (5). The women had failed to achieve glucose goals with diet alone. In the oral group, 6% were changed to insulin because they were unable to tolerate acarbose (gastrointestinal complaints). There was no difference in the pregnancy outcomes between the groups.
A 2002 report described the use of acarbose (200 mg/day) in early pregnancy (6). A 35-year-old woman with several diseases (hypertension, diabetes mellitus, hypercholesterolemia, anxiety disorder, epilepsia, and morbid obesity) conceived while being treated with multiple drugs: rosiglitazone, gliclazide (a sulfonylurea), atorvastatin, spironolactone, hydrochlorothiazide, carbamazepine, thioridazine, amitriptyline, chlordiazepoxide, and pipenzolate bromide (an antispasmodic). Her pregnancy was diagnosed in the 8th week of gestation and all medications were stopped. She was treated with methyldopa and insulin for the remainder of her pregnancy. At 36 weeks’ gestation, a repeat cesarean section delivered a healthy, 3.5-kg female infant with Apgar scores of 7 and 8 at 1 and 5 minutes, respectively. The infant was developing normally after 4 months (6).
BREASTFEEDING SUMMARY
No studies describing the use of acarbose during human lactation have been located. Because the drug acts within the gastrointestinal tract to slow the absorption of ingested carbohydrates, and <2% of a dose is absorbed systemically, the amount of unmetabolized drug in the mother’s circulation available for transfer to the milk is probably clinically insignificant. As with all drugs, however, the safest course while taking acarbose is not to breastfeed until data on its safety during lactation are available.
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. Precose. Bayer Corporation, 1997.
4.Wilton LV, Pearce GL, Martin RM, Mackay FJ, Mann RD. The outcomes of pregnancy in women exposed to newly marketed drugs in general practice in England. Br J Obstet Gynaecol 1998;105:882–9.
5.De Veciana M, Trail PA, Evans AT, Dulaney K. A comparison of oral acarbose and insulin in women with gestational diabetes mellitus (abstract). Obstet Gynecol 2002;99(Suppl):5S.
6.Yaris F, Yaris E, Kadioglu M, Ulku C, Kesim M, Kalyoncu NI. Normal pregnancy outcome following inadvertent exposure to rosiglitazone, gliclazide, and atorvastatin in a diabetic and hypertensive woman. Reprod Toxicol 2004;18:619–21.