The role of adding metformin in insulin-resistant diabetic pregnant women: a randomized controlled trial.
OBJECTIVE
The aim of the present study is to assess the impact of adding oral metformin to insulin therapy in pregnant women with insulin-resistant diabetes mellitus.


METHODS
The current non-inferiority randomized controlled trial was conducted at Ain Shams University Maternity Hospital. The study included pregnant women with gestational or pre-existing diabetes mellitus at gestations between 20 and 34 weeks, who showed insulin resistance (defined as poor glycemic control at a daily dose of ≥1.12 units/kg). Recruited women were randomized into one of two groups: group I, including women who received oral metformin without increasing the insulin dose; and group II, including women who had their insulin dose increased. The primary outcome was maternal glycemic control. Secondary outcomes included maternal bouts of hypoglycemia, need for another hospital admission for uncontrolled diabetes during pregnancy, gestational age at delivery, mode of delivery, birth weight, birth trauma, congenital anomalies, 1- and 5-min Apgar score, neonatal hypoglycemia, need for neonatal intensive care unit (NICU) admission and adverse neonatal outcomes.


RESULTS
A total number of 154 women with diabetes mellitus with pregnancy were approached; of them 90 women were eligible and were randomly allocated and included in the final analysis. The recruited 90 women were randomized into one of two groups: group I (metformin group) (n = 46), including women who received oral metformin in addition to the same initial insulin dose; and group II (control group) (n = 44), including women who had their insulin dose increased according to the standard protocol. The mean age of included women was 29.84 ± 5.37 years (range 20-42 years). The mean gestational age at recruitment was 28.7 ± 3.71 weeks (range 21-34 weeks). Among the 46 women of group I, 17 (36.9 %) women reached proper glycemic control at a daily metformin dose of 1,500 mg, 18 (39.2 %) at a daily dose of 2,000 mg, while 11 (23.9 %) received metformin at a daily dose of 2,000 mg without reaching proper glycemic control and needed raising the dose of insulin dose.


CONCLUSIONS
Adding metformin to insulin therapy in women with insulin-resistant diabetes mellitus with pregnancy seems to be effective in proper glycemic control in a considerable proportion of women, along with benefits of reduced hospital stay, reduced frequency of maternal hypoglycemia as well as reduced frequency of neonatal hypoglycemia, NICU admission and neonatal respiratory distress syndrome.
Ain-Shams Faculty of Medicine, Abbasiya Square, Cairo, Egypt, mi_monem@yahoo.com.
Moustafa Ibrahim
MI
Ibrahim
Ahmed
A
Hamdy
Adel
A
Shafik
Salah
S
Taha
Mohammed
M
Anwar
Mohammed
M
Faris
D000284:Administration, Oral; D000328:Adult; D001724:Birth Weight; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D016640:Diabetes, Gestational / Q000188:drug therapy; D004534:Egypt; D005215:Fasting / Q000097:blood; D005260:Female; D005865:Gestational Age; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D008687:Metformin / Q000008:administration & dosage* / Q000627:therapeutic use; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011254:Pregnancy in Diabetics / Q000188:drug therapy*; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin