Metformin improves blood sugar and pregnancy outcomes in diabetic women: Lancet
Canada: Metformin is increasingly being used in women with type 2 diabetes during pregnancy, little data exist on the benefits and harms of metformin use on pregnancy outcomes in these women.
The use of metformin in pregnant women with type 2 diabetes (T2D) is associated with improved pregnancy outcomes in addition to better blood sugar control, suggests a recent study in the journal Lancet Diabetes and Endocrinology. According to the study, the women who received metformin showed several maternal glycemic and adiposity benefits. The benefits include improved blood sugar control, reduced maternal weight gain and insulin dosage, lower infant size measurements, and adiposity.
There is little data on the benefits and harms of metformin use on pregnancy outcomes in T2D pregnant women despite the fact that metformin is increasingly being used in such women. Therefore, Prof Denice S Feig, Mount Sinai Hospital, Toronto, Canada, and colleagues investigated the effects of metformin addition to a standard insulin regimen on neonatal mortality and morbidity in pregnant women having type 2 diabetes.
The study involved 502 women with type 2 diabetes from 25 centers in Canada and four in Australia. They were randomized to receive either metformin 1000 mg twice daily (n=253) or placebo (n=249) in addition to insulin. It included women having type 2 diabetes who were on insulin and had a singleton viable pregnancy and in their 6-22 weeks plus 6 days gestation.
The participants were asked to check their fasting blood sugar level before the first meal of the day, before the last meal of the day, and 2 h after each meal. Study visits were done monthly and patients were seen every 1–4 weeks as was needed for standard clinical care. At these visits, body weight and blood pressure were measured. Patients were asked about tolerance to their pills, insulin doses, severe hypoglycemia events, and any hospitalizations.
The primary outcome was a composite of fetal and neonatal outcomes, for which the researchers calculated the relative risk and 95% CI between groups, stratifying by site and BMI using a log-binomial regression model with an intention-to-treat analysis. Secondary outcomes included several relevant maternal and neonatal outcomes.
Key findings of the study include:
- Complete data were available for 233 (92%) participants in the metformin group and 240 (96%) in the placebo group for the primary outcome.
- There were no significant difference in the primary composite neonatal outcome between the two groups (40% vs 40%; relative risk [RR] 1·02).
- Compared with women in the placebo group, metformin-treated women achieved better glycaemic control (HbA 1c at 34 weeks' gestation 41·0 mmol/mol vs 43·2 mmol/mol; 5·90% vs 6·10%; mean glucose 6·05 vs 6·27), required less insulin (1·1 units per kg per day vs 1·5 units per kg per day; difference, gained less weight (7·2 kg vs 9·0 kg) and had fewer caesarean births (125 [53%] of 234 in the metformin group vs148 [63%] of 236 in the placebo group; relative risk [RR] 0·85).
- There found no significant difference between the groups in hypertensive disorders (55 [23%] in the metformin group vs 56 [23%] in the placebo group; RR 0·99).
- Compared with those in the placebo group, metformin-exposed infants weighed less (mean birthweight 3156 g vs 3375 g; difference −218, fewer were above the 97th centile for birthweight (20 [9%] in the metformin group vs 34 [15%] in the placebo group; RR 0·58), fewer weighed 4000 g or more at birth (28 [12%] in the metformin group vs 44 [19%] in the placebo group; RR 0·65), and metformin-exposed infants had reduced adiposity measures (mean sum of skinfolds 16·0 mm vs 17·4 mm; mean neonatal fat mass 13·2 vs 14·6).
- 30 (13%) infants in the metformin group and 15 (7%) in the placebo group were small for gestational age (RR 1·96).
- We found no significant difference in the cord c-peptide between groups (673 pmol/L  in the metformin group vs 758 pmol/L  in the placebo group).
- The most common adverse event reported was gastrointestinal (38 events in the metformin group and 38 events in the placebo group).
"We found several maternal glycaemic and neonatal adiposity benefits in the metformin group including reduced maternal weight gain and insulin dosage and improved glycaemic control, the lower adiposity, and infant size measurements. This resulted in fewer large infants but a higher proportion of small-for-gestational-age infants," wrote the authors.
"Understanding the implications of these effects on infants will be important to properly advise patients who are contemplating the use of metformin during pregnancy," they concluded.
The study, "Metformin in women with type 2 diabetes in pregnancy (MiTy): a multicentre, international, randomised, placebo-controlled trial," is published in the journal Lancet Diabetes and Endocrinology.