Metformin and insulin for the treatment of gestational diabetes
Gestational diabetes complicates around 5% of pregnancies and its incidence is on rise. Gestational diabetes is associated with increased complications during pregnancy. It is also associated with long-term risk of diabetes in both mother and offspring.1,2
Insulin is used as first line drug in gestational diabetes treatment. Insulin is classified as FDA category B drug means animal reproduction studies have failed to demonstrate a risk to the foetus and there are no adequate and well-controlled studies in pregnant women. FDA approved metformin in year 1994 long after it was approved in many countries for the treatment of type 2 diabetes. Metformin has also been used extensively in patients of infertility with PCOS; as a result many patients continued it inadvertently in first trimester of pregnancy therefore having large safety data in pregnancy. Metformin too categorized as US FDA pregnancy category B, at par with insulin.
Recently FDA approved insulin detemir (Levemir, Novo Nordisk) with pregnancy Category B classification. Previously, Levemir was relegated to pregnancy category C, meaning animal reproductive studies has shown an adverse effect on the fetus and adequate and well-controlled studies in humans were not available. FDA changed Levemir’s status after receiving a new randomized, controlled trial of 310 pregnant women with type 1 diabetes. The study compared the safety and efficacy of Levemir against NPH insulin.
Insulin is a big market with annual turnover of several billion dollar in human insulin and insulin analogues. Apart from type 1 diabetes, pregnancy with diabetes is “absolute indication” of insulin. Although data of thousands of pregnancies are available in which metformin was used safely there are no clear guideline for use of metformin in pregnancy with diabetes (type2 or gestational). Status quo favours select insulin producing pharmaceutical companies.
In a MIG trial published in NEJM 3, involving more than 700 patients suggested that metformin, alone or with supplemental insulin, is an effective and safe treatment option for women with gestational diabetes mellitus who meet the usual criteria for starting insulin.It also confirmed that metformin is more acceptable to patients with gestational diabetes mellitus than is insulin.
Had metformin been a patented drug we would have seen many new trial supporting its use in pregnancy. Regulatory authorities/ government should promote large trial to provide definitive answers to this question so that millions of diabetic pregnant females can have safe, cheaper alternative and be spared of daily pain of insulin needle.
1. Ben-Haroush A, Yogev Y, Hod M. Epidemiology of gestational diabetes mellitus and its association with Type 2 diabetes. Diabet Med 2004;21:103-113
2. Silverman BL, Metzger BE, Cho NH, Loeb CA. Impaired glucose tolerance in adolescent offspring of diabetic mothers: relationship to fetalhyperinsulinism. Diabetes Care 1995;18:611-617
3. Rowan JA, Hague WM, Gao W, Battin MR, Moore MP; MiG Trial Investigators.Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med.2008 May 8;358(19):2003-15. doi: 10.1056/NEJMoa0707193. Erratum in: N Engl J Med.2008 Jul 3;359(1):106. PubMed PMID: 18463376.
Competing interests: No competing interests