CASE STUDY

Professor Fidelma Dunne, Associate Director of the HRB-Clinical Research Facility Galway leads a clinical study called EMERGE

Diabetes (high blood sugars) developing during pregnancy is called Gestational Diabetes Mellitus (GDM). GDM is increasing, affecting one-in-eight pregnant women in Ireland (12%). Adverse outcomes related to GDM continue despite current management. Macrosomia (birth weight >4kg) occur in about 20% of babies. Macrosomic babies are more at risk of low blood sugars, breathing problems, jaundice and birth injuries necessitating admission to neonatal unit care (26% GDM vs 9% normal pregnancies). Long-term, such babies are at increased risk of obesity and diabetes.

Mothers with GDM have a 2-fold increased risk of developing a pregnancy related hypertensive disorder and delivery by Caesarean section is increased by 30%. Long term mothers have a 7-fold greater chance of developing Type 2 diabetes. Pre-pregnancy maternal body mass index (BMI) in addition, increases these risks. We and others have demonstrated that excessive gestational weight gain (GWG) is an important additional risk factor for adverse pregnancy outcome.

Professor Fidelma Dunne. Associate Director of the Clinical Research Facility, Galway; Professor of Medicine and Consultant Endocrinologist at Galway University Hospitals group

Professor Fidelma Dunne. Associate Director of the Clinical Research Facility, Galway; Professor of Medicine and Consultant Endocrinologist at Galway University Hospitals group

The first line of managing high blood sugar levels is dietary change and exercise.

However at least 40% of women with GDM will require insulin to maintain normal blood sugar levels. While insulin is effective at keeping blood sugars in the normal range, it has important side-effects and limitations for the mother (e.g. excessive weight gain, low blood sugars, higher chance of delivery by caesarean section) and baby (tendency to excess weight at birth and more likely to require NICU admission).

A potential other treatment is a tablet called metformin.

Metformin has been used for 30 years in the treatment of Type 2 diabetes. It is also used in women with polycystic ovary syndrome (PCOS) who are having trouble with fertility. In addition, it has been shown to be effective in reducing progression to Type 2 diabetes in those at high risk or those with pre-diabetes. Metformin is as effective as insulin and safe when used in pregnancy in women with Polycystic Ovary Syndrome (PCOS), Obesity and GDM with BMI > 30.

At NUI Galway we wish to explore if metformin is effective for managing all women with GDM (not just those who are obese) if started close to the time of a GDM diagnosis in addition to diet and exercise. We also want to see also if metformin is associated with less excessive maternal weight gain, less need for NICU care for babies of mothers with GDM, less post-partum glucose intolerance for the mother and if it is more cost effective and more acceptable to women. We are evaluating this in a double-blind placebo controlled randomized trial called EMERGE (Effectiveness of MEtformin in addition to usual care in the Reduction of Gestational diabetes mellitus Effects).

This trial is funded by the HRB and is only possible to conduct through the infrastructure of the CRF which has helped the trial team to work from the conception of the trial through ethics and HPRA submissions, pharmacovigilance, data safety and monitoring and eventually the analysis of the trial findings. The clinical team are also resident in the CRF and this is where women with GDM attend for their trial visits.

We need to recruit 550 women into the trial and the response of women has been tremendous. We have already recruited 440 women and despite COVID and with the help of the CRF we have been able to continue with the trial and remain on target. We now have women entering the trial on their second pregnancy. We hope to have all women recruited by April 2022 and have the results available at the end of 2022.

If positive, EMERGE will change clinical practice by providing evidence to support early active management with metformin at the time of diagnosis in a broader GDM population.