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MS WordPerinatologist Corner - C.E.U/C.M.E. Modules
Diabetes In Pregnancy Series
Sponsored by The Indian Health Service Clinical Support Center
PART 2: Management, delivery, and postpartum
6. How about alternatives to insulin?
Please note that the Cochrane Library finds there appears to be no clear evidence of benefit from very tight glycemic control for pregnant diabetic women. Since very strict control may have a substantial impact on lifestyle, this suggests caution in advising such a degree of control.
The Cochrane Library also finds a comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomized clinical trials. The story of the introduction of human might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety.
Some patients will be reluctant to give themselves multiple daily insulin injections and it would be convenient to be able to offer them an alternative. Classic teaching is that oral hypoglycemic agents can cause severe hypoglycemia during pregnancy and are to be avoided. Currently, investigation is in progress on the use of oral hypoglycemic agents in pregnancy, but their use at this time can not yet be considered standard of care.
The agent that has been most extensively studied in pregnancy is the sulfonylurea, glyburide. Level I results have been encouraging to date. (Langer et al) Glyburide does not cross the placenta because of its molecular size. Hence, like insulin, it will control the maternal blood sugar without affecting fetal glucose homeostasis. Nevertheless, its mode of action, stimulating secretion of insulin from the pancreatic islet cells, probably does not well address the underlying pathophysiology of this disorder, which is characterized by insulin resistance and hyperinsulinemia.
Metformin, a biguanide, would seem to be an ideal choice from a physiologic standpoint since it works at the “post-receptor” level to enhance glucose utilization. Metformin is a small molecule and readily crosses the placenta. This fact has limited its investigation in pregnancy. Nevertheless, metformin should not cause hypoglycemia in euglycemic subjects, and fetal effects should theoretically be minimal. There is a small body of experience with the drug in patients with infertility secondary to polycystic ovaries. These patients have conceived on metformin, and then continued it during pregnancy. (Glueck et al) At the present time, it cannot be recommended for clinical use.
Acarbose, because it works locally in the gut to decrease glucose absorption, might also be expected to be safe in pregnancy, but its effects are limited by its side effects of bloating and diarrhea. Insulin therefore remains the standard of care for those patients who cannot maintain euglycemia on medical nutrition therapy.
