The care of pregestational and gestational diabetes and drug metabolism considerations

ABSTRACT

Introduction: Normal pregnancy development involves gradual decline in insulin sensitivity, which sometimes requires pharmacotherapy. Insulin is the drug of choice for gestational and pregestational diabetes. Metabolism of traditional insulins results in inadequate onset and duration of action and marked peak activity. These properties increase risk of excessive glucose excursions, which are especially undesirable during pregnancy. Insulin analogs have been emerging as a safer and more effective treatment of diabetes during pregnancy.

Areas covered: This manuscript reviews currently used antihyperglycemic agents: fast and long-acting insulins, metformin and glyburide. Trials demonstrating their efficacy and safety during pregnancy are described. Certain drug metabolism considerations (e.g. affinity to IGF-1) are emphasized.

Expert opinion: The theories that insulin analogs bind to immunoglobulin and cross placenta have been disproved. Lispro, aspart, glargine and detemir do not transfer across the placenta and do not result in adverse maternal and neonatal outcomes. In addition, favorable pharmacokinetic profiles (rapid onset and 24-hour near peakless activity) substantially reduce blood glucose variability including hypoglycemia. We believe that insulin analogs should be given strong consideration for the treatment of diabetes during pregnancy. Metformin has also proven to be safe and may be considered as an initial single agent for milder gestational diabetes.

KEYWORDS:

• Diabetes
• fetal
• insulin
• metabolism
• maternal
• pregnancy

Article highlights

• The prevalence of hyperglycemia in pregnancy has been estimated at ≈17% globally.

• Diet and exercise is an effective combination for improving glycemia and is routinely recommended for most pregnant women.

• Conventional treatment strategies include the oral agent glyburide and traditional insulin preparations: regular insulin and NPH.

• Favorable pharmacokinetic profile of insulin analogs (faster onset, longer duration, no peak) warranted randomized controlled trials in pregnant women to investigate safety and efficacy of these agents in pregestational and gestational diabetes.

• Metabolism of insulins, glargine and lispro involves increased affinity to insulin like growth factor 1, which regulates fetal growth and development.

• Although metformin readily transfers across the placenta, the oral agent has been demonstrated to be safe in pregnancy.

• Glyburide is excessively metabolized by hepatic and placental microsomes and has been shown to result in fetal complications.

• Metformin may be considered as an initial single agent for milder gestational diabetes and insulin analogs (glargine or detemir - basal and lispro or aspart - prandial) for the other types of diabetes during pregnancy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper is not funded.