Exploring an alternative to insulin to manage Diabetes in pregnancy
Ahead of World Diabetes Day on 14 November, Professor Fidelma Dunne (Principal Investigator with Diabetes Collaborative Clinical Trials Network Ireland, a HRB research network to enhance diabetes care and outcomes), discusses the EMERGE trial for Gestational Diabetes Mellitus (GDM) or diabetes in pregnancy. This trial is taking place at and coordinated by Clinical Research Facility Galway, a HRB centre supporting clinical trials to improve health and care.
4 min read - 12 Nov 2021
Recently, I was delighted to lead a successful application to the Health Research Board (HRB) for funding to support an all-island Diabetes Collaborative Clinical Trials Network Ireland. Our aim is to improve health and wellbeing for patients with diabetes through research and an active portfolio of ambitious multi-centre trials on the island of Ireland. Regardless of geographical location or socioeconomic status, all patients will be facilitated to take part in relevant trials through a well-developed network of clinical sites supported by Clinical Research Facilities/Centres (CRF/Cs), academic institutions and the National Clinical Care programme in Diabetes.
Focus on Gestational Diabetes Mellitus (GDM)
As mentioned, the focus topic for this blog is Gestational Diabetes Mellitus (GDM), which is diabetes (high blood sugars) that develops during pregnancy. GDM is increasing, now affecting one-in-eight pregnant women in Ireland (12%), with adverse outcomes continuing despite current management. For example, macrosomia (birth weight greater than 4kg) occurs in about 20% of babies, which leaves them more at risk of low blood sugars, breathing problems, jaundice and birth injuries necessitating admission to neonatal unit care. Long-term, such babies are at increased risk of obesity and diabetes.
Furthermore, mothers with GDM have a two-fold increased risk of developing a pregnancy-related hypertensive disorder, and delivery by Caesarean section is increased. Long term, mothers have a seven-fold greater chance of developing Type 2 diabetes. Being overweight pre-pregnancy also increases these risks. We and others have demonstrated that excessive gestational weight gain (GWG) is an important additional risk factor for adverse pregnancy outcome.
Metformin – an alternative to insulin
The first line of managing high blood sugar levels is dietary change and exercise. However, at least 40% of women with GDM will also require insulin to maintain normal blood sugar levels. While insulin is effective for this, it has side-effects and limitations for the mother (e.g., tendency towards excess weight gain, increased risk of low blood sugars, greater chance of delivery by caesarean section) and baby (more likely to require Neonatal Intensive Care Unit admission).
A potential alternative treatment is metformin, which has been used for over 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.
The EMERGE trial
At NUI Galway our team will explore if metformin is an effective alternative 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 will result in 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 acceptable to women. We are evaluating this in a double-blind placebo controlled randomized trial (a medical study involving two groups of human participants in which neither group knows who’s getting what treatment and placebo are given to a control group) 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 HRB-funded Clinical Research Facility Galway (CRFG). Recruitment to the trial is already underway, and the response has been tremendous. Despite COVID, and with the help of CRFG, we have so far recruited 440 (80%), managed to continue the trial and remain on target. We now have women entering the trial on their second pregnancy, and hope to have full recruitment by April 2022, and results available at the end of the same year. If positive, EMERGE will change clinical practice by providing evidence to support early active management with metformin at the time of diagnosis among women who develop Diabetes during pregnancy.
About the author: Fidelma Dunne is a Professor in Medicine at the National University of Ireland (NUIG), a Consultant Endocrinologist at Galway University Hospitals group, and Principal Investigator with Diabetes Collaborative Clinical Trials Network Ireland, a HRB research network to enhance diabetes care and outcomes. Her major research interest is in the area of pregnancy and diabetes.
Find out more:
More about Clinical Research Facility Galway
Clinical Research Facility Galway on Twitter
4 min read - 12 Nov 2021