Miglitol in Pregnancy and Breastfeeding
Fetal Risk Summary
Miglitol is an oral a-glucosidase inhibitor, in the same class as acarbose (see Acarbose), that delays the digestion of ingested carbohydrates within the gastrointestinal tract, thereby reducing the rise in blood glucose following meals (1). It is used either alone or in combination with a sulfonylurea as an adjunct to diet in the management of type II diabetes (noninsulin-dependent diabetes mellitus). In contrast to acarbose, miglitol is readily absorbed into the systemic circulation, but the absorption is saturable at high doses. In addition, miglitol is not metabolized and is excreted unchanged in the urine with a elimination half-life of approximately 2 hours (1).
Reproduction studies have been conducted in animals with miglitol. In rats and rabbits at doses up to 12 and 10 times, respectively, the maximum recommended human exposure based on body surface area (MRHE), no evidence of teratogenicity was observed. In addition, no evidence of impaired fertility or fetal harm were noted at doses up to 4 and 3 times the MRHE, respectively, in these species. At 12 and 10 times the MRHE in rats and rabbits, respectively, maternal and/or fetal toxicity were noted. In rats, fetotoxicity was characterized by a slight but significant reduction in fetal weight. In rabbits, a slight reduction in fetal weight, an increased number of nonviable fetuses, and delayed ossification of the fetal skeleton were evident. In the rat peri-postnatal study, an increase in stillborns occurred at 4 times the MRHE (1).
Placental transfer of miglitol has been documented in pregnant rats after oral administration (2). It is not known if miglitol crosses the human placenta, but the molecular weight (about 207) is low enough that transfer to the fetus should be expected.
No reports describing the use of miglitol during human pregnancy have been located. Miglitol is normally used either alone or in combination with oral hypoglycemic agents, and these hypoglycemic drugs are not indicated for the pregnant diabetic as they may not provide good control in patients who cannot be controlled by diet alone. Carefully prescribed insulin therapy provides better control of the mother's glucose, thereby preventing the fetal and neonatal complications that occur with this disease. 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 effect the fetus. 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, most experts, including the American College of Obstetricians and Gynecologists, recommend that insulin be used for types I and II diabetes occurring during pregnancy and, if diet therapy alone is not successful, for gestational diabetes (3,4).
Breast Feeding Summary
Miglitol is excreted into the milk of lactating rats. The mean milk:plasma ratio, based on area under the concentration curve, was 1.3 (2). Consistent with its relatively low molecular weight (about 207), miglitol is also excreted into human milk (1). The total amount excreted, however, is very small, accounting only for 0.02% of a 100-mg dose (only 50%70% of a 100-mg dose is bioavailable) (1). The estimated exposure of a nursing infant was about 0.4% of the mother's dose. The effects of this exposure on a nursing infant are unknown, but the manufacturer recommends that miglitol not be used during lactation (1). A 2000 review also stated that miglitol should not be used during breast feeding (5).
- Product information. Glyset. Pharmacia & Upjohn, 2000.
- Ahr H-J, Boberg M, Brendel E, Krause HP, Steinke W. Pharmacokinetics of miglitol. Absorption, distribution, metabolism, and excretion following administration to rats, dogs, and man. Arzneim-Forsch/Drug Res 1997;47:73445.
- American College of Obstetricians and Gynecologists. Diabetes and pregnancy. Technical Bulletin. No. 200, December 1994.
- Coustan DR. Management of gestational diabetes. Clin Obstet Gynecol 1991;34:55864.
Campbell LK, Baker DE, Campbell RK. Miglitol: assessment of its role in the treatment of patients with diabetes mellitus. Ann Pharmacother 2000;34:1291301.
Questions and Answers
which is better alpha glucosidase inhibitor than miglitol? why miglitol is better than other?, IN TYPE 2 DIBETES WHICH IS BETTER OPTION TO CONTROLE PPG
Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates (such as starch and table sugar). Carbohydrates are normally converted into simple sugars (monosaccharides) which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of carbohydrates on blood sugar.
Examples of alpha-glucosidase inhibitors include:
* Acarbose- Precose®
* Miglitol - Glyset®
Even though the drugs have a similar mechanism of action, there are subtle differences between acarbose and miglitol. Acarbose is an oligosaccharide, whereas miglitol resembles a monosaccharide. Miglitol is fairly well-absorbed by the body, as opposed to acarbose. Moreover, acarbose inhibits pancreatic alpha-amylase in addition to alpha-glucosidase.
Miglitol is used, alone or with other drugs, to treat type 2 diabetes (condition in which the body does not use insulin normally and, therefore, cannot control the amount of sugar in the blood), particularly in people whose diabetes cannot be controlled by diet alone. It slows the breakdown and absorption of table sugar and other complex sugars in the small intestine. This process results in decreased blood sugar (hypoglycemia) levels following meals.