Insulin glargine in pregnancy

I chose this controversial topic because I am interested in hearing others’ thoughts on the matter.

Recently, a series of studies were published raising the question of possible increased risk for malignancy with insulin glargine (Lantus, Sanofi-Aventis) compared to other insulins. Although the literature remains inconclusive, this controversy reminded me of earlier concerns regarding the use of insulin glargine in pregnancy. Soon after its release, questions were raised regarding increased affinity of glargine for the insulin-like growth factor I receptor compared with other insulins. Could this be clinically significant?

Initial teratogenic reproductive studies were performed in rats and rabbits. There were five rabbit fetuses from two litters in the high-dose group (approximately twice the recommended human starting dose) which exhibited dilation of cerebral ventricles. Fertility and embryonic development were normal. However, retrospective/observational studies have not seen increased adverse maternal or neonatal outcomes in humans treated with insulin glargine during pregnancy compared to other insulins.

Insulin therapy is standard of care in patients with diabetes who are pregnant. Insulin glargine is not approved by the FDA for use in pregnancy; however, there is currently no insulin with a formal on-label indication for use in pregnancy. Some insulins, including aspart, lispro, regular and NPH, are generally regarded as safe and are pregnancy category “B.” Insulin glargine as well as detemir, however, are pregnancy category “C,” which means these agents should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There are widely differing opinions regarding the use of insulin glargine in pregnancy. When I ask colleagues whether they use insulin glargine in pregnancy, responses range from: “We do it all the time, is there a problem?” to “Oh no! We would never do that! You don’t use insulin glargine in pregnancy — do you?” What I find curious is how some obstetricians who avoid insulin glargine in pregnancy have absolutely no problem using oral agents such as glyburide and/or metformin. This is also off-label prescribing with unknown effects.

When insulin glargine was first released, I switched many of my pregnant patients with diabetes over to multiple doses of NPH for basal insulin coverage. This regimen worked reasonably well. In an ideal situation, however, patients who require intensive insulin during pregnancy are best managed with a continuous subcutaneous insulin infusion pump (preferably initiated before pregnancy).

Nevertheless, there are many who cannot go on an insulin pump because of insurance limitations or personal preference. In these patients, particularly those who are already on insulin glargine with excellent control, I am hesitant to switch to another basal insulin purely because of theoretical concerns. It is not that I do not think such concerns are valid. Indeed, the issue of basal insulin analogs in pregnancy must be investigated further.

I am hesitant to switch because of the real harm that can occur from poorly controlled diabetes during pregnancy. It is difficult for me to put the fetus at risk by changing to another regimen that may or may not be as effective without stronger rationale to do so.

I am interested in hearing your thoughts on this issue. Is this a concern for you? What are you telling your patients? What are you doing in your own practices?

Gallen IW. Diabet Med. 2008;25:165-169.

Fang YMV. Journal Matern Fetal Neonatal Med. 2009;22:249-253.

Henderson CE. Reprod Med. 2009;54:208-210.