GUARD
Research type
Research Study
Full title
Randomised controlled trial of Gestational treatment with Ursodeoxycholic Acid compared to Metformin to Reduce effects of Diabetes mellitus
IRAS ID
1003208
Contact name
Caroline Ovadia
Contact email
Sponsor organisation
King's College London
Eudract number
2019-002880-82
Research summary
: Randomised controlled trial of Gestational treatment with Ursodeoxycholic Acid compared to metformin to Reduce effects of Diabetes mellitus GUARD TRIAL LAY SUMMARY
Purpose
Gestational diabetes happens in pregnancy when a mother’s blood glucose is higher than normal. The GUARD trial compared a new treatment with a medicine that we normally use.
High glucose in pregnancy can increase the baby’s growth. So, we aim to keep mother’s glucose below a target level. Firstly, mothers make changes to their diet and exercise to lower their blood glucose. If the glucose is still high, we give medicines to help. In the UK, we use the medicine metformin first. However, some people are worried that metformin may cause increased growth and size for children later in life.
UDCA is a safe medicine in pregnancy; its full name is ursodeoxycholic acid. We already use UDCA to treat a liver condition in pregnancy. We found that people taking UDCA have lower blood glucose. We wanted to compare metformin with UDCA in gestational diabetes, to see if UDCA is better at lowering blood glucose. We planned to treat 79 patients with each medicine.What happened?
The study started during the COVID-19 pandemic. There were delays and difficulties with patient recruitment. So, we stopped the main GUARD study with only four participants. We did not compare their results due to the small numbers.However, we did continue part of the study, called GUARD-MEC. This looked at how gestational diabetes and metformin affect gut hormones. Gut hormones are small messengers that the intestine produces. They send messages from the intestine to other organs, like the pancreas, liver, and fat. They help to control how the body stores and releases glucose and fats. One of the main gut hormones that lowers glucose is GLP1.
We took blood from pregnant people before and three times after food. We measured levels of a variety of gut hormones, including GLP1, in the blood. We compared what happens to people without gestational diabetes to those with gestational diabetes. We compared what happens when people used only diet changes and exercise to treat their diabetes with what happens when people also use metformin.Results
51 people took part in GUARD-MEC. We found that GLP1 levels in the blood were similar between participants. However, our results suggested that people with gestational diabetes taking metformin may have higher levels of GLP1 than those without diabetes. We think that this means that patients with gestational diabetes taking metformin have stronger messages from the intestine to tell the pancreas to lower glucose. It may also mean that patients with gestational diabetes may respond less well to gut hormone signals. This could explain why some patients get gestational diabetes.What this means for patients
People with gestational diabetes taking metformin had better glucose control than those only using diet and exercise. This may suggest that more patients would benefit from metformin than we are currently giving this to.Kings College London and Guy’s and St Thomas’ NHS Trust managed this study. The Jon Moulton Charity kindly funded the research. You can ask for further information from caroline.ovadia@kcl.ac.uk.
We are incredibly grateful to the 55 participants (and their babies) for taking part. This will help us to understand diabetes better. It will also improve treatments for future patients with gestational diabetes.
Each year in the UK approximately 35,000 women develop diabetes during pregnancy, a
condition called gestational diabetes mellitus (GDM), which increases the risk of adverse
outcomes for both mother and child. Metformin, although unlicensed for used in
pregnancy, is the most commonly used first line pharmacological treatment. However,
there is increasing concern about its widespread use during pregnancy, because of its
limited efficacy and because of potential safety concerns. Other common treatments have
not been shown to be superior. Therefore, there is an unmet need for additional
therapies.
Ursodeoxycholic acid (UDCA) is commonly used in pregnancy for the treatment of
intrahepatic cholestasis of pregnancy. It is currently not an established/licensed
treatment for GDM. However data from observational studies of women with cholestasis
in pregnancy has flagged this to be a potential effective treatment to control blood
glucose levels in GDM.
GUARD is a Clinical Trial that wants to explore the impact of UDCA compared to
metformin in the treatment of GDM. We want to recruit 158 women who are overweight
or obese who have been diagnosed with GDM, and require pharmacological treatment.
Glucose control is our primary measure. We will ask women to attend three study visits,
which will coincide with the time of their antenatal appointments. We want to collect a
range of clinical and research blood samples, to measure quality of life and treatment
satisfaction through two questionnaires, and we will ask women to wear a continuous
glucose monitor for three 10 day periods.
There will be a number of optional assessments that participants will be offered. The
primary outcome will be the fasting blood glucose concentration at 36 weeks of gestation.
We intend to carry out this study at 3 sites (Guy’s and St Thomas, Imperial College and
Nottingham), and it has been funded by a J.P Moulton Foundation grant.REC name
London - Westminster Research Ethics Committee
REC reference
20/LO/0504
Date of REC Opinion
5 May 2020
REC opinion
Further Information Favourable Opinion