A large trial found that giving obese pregnant women the diabetes drug, metformin, to prevent heavier babies, had no effect compared with an inactive dummy tablet. The trial was funded by the NIHR and Medical Research Council, and was the first to give metformin, a diabetes drug that is safe in pregnancy, to pregnant women without type 2 diabetes for this purpose.
There are theoretical reasons why the medication may help in reducing a baby’s birthweight and previous studies had shown links between higher glucose levels in mother’s blood and larger babies. Participants received either standard doses of metformin or the inactive tablet from about 12 weeks of a mother’s pregnancy to a baby’s birth. The researchers now aim to track the children’s weight and health beyond birth to see if there are any other long-term benefits or side-effects. For now, the results show metformin does not work for this purpose.
Why was this study needed?
Almost a quarter of women (24%) were obese in 2013 in England. This is up from 16% 20 years earlier. Obese pregnant women are more likely than other women to give birth to heavier babies, and some evidence suggests these babies are more likely to become obese adults. The causes of increased birthweight are not clear, but the mother’s blood sugar control may be a factor. Metformin - a drug taken by mouth – is used to help control the blood sugar of people with type 2 diabetes. This study aimed to find out whether giving metformin to obese pregnant women could prevent their babies being born heavy. Some studies have looked at women who develop diabetes in pregnancy, but this was the first study using metformin in this way in pregnant women without type 2 diabetes.
What did this study do?
This randomised controlled trial took place at 15 NHS antenatal clinics. It included 449 obese pregnant women (BMI greater than or equal to 30 kg per square metre) who had normal blood sugar control when recruited to the trial at 12 to 16 weeks of pregnancy. They were randomly assigned to take either metformin or inactive placebo every day until birth. Birthweight centile, a measure standardised by length of pregnancy, sex, and number of previous babies and derived from weight charts, was used for this study. It is a marker of ill health in later life.
Neither the women nor the treating healthcare staff knew who was being given metformin or placebo. The results for all women were analysed according to the treatment group they had been randomised to, regardless of whether or not they completed the trial. Both points reduce bias and improve the reliability of the results. However, more than a third of women did not take metformin as prescribed. This may hide any positive effect seen in the women who did take it as prescribed.
What did it find?
- Metformin had no effect on the birthweight of babies compared with placebo. Average birthweight was very similar in the two groups (3,462 g given metformin vs. 3,463 g given placebo) as was the proportion of babies born overweight or obese. 14% of babies were overweight in the group taking metformin compared to 17% in the placebo group. Taking into account adjustments for length of pregnancy and sex of the baby, these differences were not statistically different.
- There were no differences in blood sugar levels near the end of pregnancy (36 weeks) between women given metformin or placebo.
- Two moderate side effects were significantly more common in the metformin group: diarrhoea (42% compared to 19% in the placebo group) and vomiting (32% compared to 22%). There was no significant difference in the number of serious events – such as miscarriage - between the groups.
- Only two thirds of women recorded taking their medication as prescribed (227 out of 344). Only 260 out of 449 women completed the trial, and the most common reasons given for not taking part were concerns that the study drugs might harm the baby, or not being aware that obesity in pregnancy was a problem.
What does current guidance say on this issue?
Metformin is not currently licensed for use in people with normal blood sugar levels, like the women in this trial.
NICE guidance from 2010 on weight management in pregnancy recommends a range of healthy lifestyle measures for obese women in pregnancy, such as taking more exercise and eating a balanced diet. NICE guidance published in 2015 on diabetes during pregnancy advises that metformin may be used during pregnancy for women with pre-existing diabetes. It may also be used for women who develop diabetes during pregnancy (gestational diabetes) where blood sugar cannot be controlled with diet and exercise.
What are the implications?
The findings of this trial do not prompt any change to existing guidance or practice. Future trials on metformin for preventing high birthweight would need to allow for a high proportion of trial participants not taking the medication as prescribed.
This trial does not support the use of metformin to improve pregnancy outcomes in obese women without diabetes. The researchers plan to track the children’s weight and health in the future, to see if there are any long term health effects into adulthood.
Chiswick C, Reynolds RM, Denison F, et al. Effect of metformin on maternal and fetal outcomes in obese pregnant women (EMPOWaR): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol. 2015.
This project was funded by the Efficacy and Mechanism Evaluation (EME) Programme, an MRC and NIHR partnership (project number 08/246/09).
HSCIC. Statistics on Obesity, Physical Activity and Diet England 2015. Leeds: Health and Social Care Information Centre; 2015.
NICE. Diabetes in pregnancy: management of diabetes and its complications from preconception to the postnatal period. NG3. London: National Institute for Health and Care Excellence; 2015.
NICE. Weight management before, during and after pregnancy. PH27. London: National Institute for Health and Care Excellence; 2010.
NICE. The management of type 2 diabetes. CG87. London: National Institute for Health and Care Excellence; 2009.
Produced by the University of Southampton and Bazian on behalf of NIHR through the NIHR Dissemination Centre