METAFOR
Research type
Research Study
Full title
METAFOR Study Pilot: Metformin Antenatal Formulations Study Pilot: an open-label feasibility study
IRAS ID
1004070
Contact name
Fiach O'Mahony
Contact email
Sponsor organisation
University of Edinburgh
ISRCTN Number
ISRCTN90686599
Research summary
Research Summary
This study aims to find an effective and well-tolerated drug therapy for pregnant women with gestational diabetes, the most common pregnancy complication.
Metformin is endorsed by National Guidelines for use as first-line drug therapy to control blood sugar levels for women with gestational diabetes. Metformin has significant advantages, including that it is a tablet and it helps limit pregnancy weight gain. However, metformin has poorly tolerated side effects including nausea and diarrhoea, which can mean that many women have to stop the tablets, or cannot tolerate higher doses of the tablets, so have to take supplemental insulin injections to control their blood sugar levels.
Metformin also freely crosses the placenta. Although no short-term adverse effects for the child have been observed, there remains uncertainty about whether there are potential long-term effects of metformin exposure for the child.
In this study we aim to test whether a new “delayed-release” metformin tablet is a feasible and acceptable drug for women with gestational diabetes. This tablet contains exactly the same ‘active ingredient of metformin’ but the way that it is packaged into a tablet means that it is absorbed lower down in the gut, rather than in the stomach, which we think will have several benefits. Results from studies using metformin delayed-release in people who are not pregnant indicate this metformin preparation will have fewer side effects. This means that women will be able to take their treatment regularly, thus improving their blood sugar control and avoiding the need for insulin injections. Due
to the delayed-release formulation, we believe there will be substantially reduced levels of metformin in the mother’s blood. This will reduce transfer of metformin across the placenta compared to standard metformin tablets, minimising the potential for adverse effects of metformin exposure for the child.End of Study Lay Summary of study results
Metformin Antenatal Formulations Study Pilot Study (METAFOR)
IRAS Number: 1004070, ISRCTN Number: 90686599METAFOR aimed to find an effective and well-tolerated drug therapy for women and birthing people
with gestational diabetes, the most common pregnancy complication.
Metformin IR (immediate release) is widely used as first-line drug therapy in the UK to control blood
sugar levels. Metformin has significant advantages, including that it is a tablet and it helps limit
pregnancy weight gain. However, standard metformin IR also has poorly tolerated side effects
including nausea and diarrhoea. Moreover, it freely crosses the placenta to the baby. There is
uncertainty about whether there could be any potential long-term effects of metformin exposure for
the child. In this pilot study we aimed to test whether a new “delayed-release” (DR) metformin tablet
could be a feasible and acceptable alternative for women with gestational diabetes. This tablet
contains exactly the same active ingredient, which is metformin. However, the new tablet gets
absorbed into the body in a lower part of the gut, rather than in the stomach. We think that this will
result in fewer side effects than regular metformin tablets (metformin IR) and substantially reduced
levels of metformin crossing the placenta to the baby.
The METAFOR study involved three ‘arms’ and aimed to recruit a total of 50 women with singleton
pregnancies and gestational diabetes:
Arm 1: Participants (women scheduled for elective Caesarean section at ≥37 weeks) were to take
one metformin DR 900 mg tablet on the morning of delivery by Caesarean section with blood,
umbilical cord and placenta sampling.
Arm 2: Participants (women between ≥28 and ≤36 weeks gestation) were to take one metformin
DR 900 mg tablet prior to serial blood and urine sampling at a clinical research facility.
Arm 3: Participants (women who are adequately treated with metformin IR at <36 weeks pregnant)
were to be randomly allocated to continue their own standard dose of metformin IR for 7 days,
followed by 7 days of metformin DR 900 mg or vice versa.
Due to unforeseen and unavoidable delays during the initial phase of this project (largely caused by
lengthy discussions regarding the drug supply agreement as well as exceptionally long Medicines and
Healthcare products Regulatory Agency review timelines), the trial opened to recruitment
approximately 12 months behind schedule. The original batch of study drug expired in December
2023 and we were unable to source additional study drug. Consequently, the trial had to be terminated
earlier than expected after being open to recruitment for only approximately three months. During that
time, 234 women were screened between two study sites, 16 women were approached and one
participant was recruited to trial Arm 1. Since this trial was terminated early with n= 1 participant, there
has been no formal analysis. However, the participant’s blood samples appear to support our
hypothesis that reduced levels of metformin DR are crossing the placenta compared to metformin IR.
While we were not able to complete the study, we have gained experience with regards to realistic
set-up timelines, and have gathered important feedback from site teams on the study documentation
and collected screening data. This will be valuable information for future studies.
Notes:
The terms 'women' and ‘birthing people’ are used in this trial’s participant facing information to refer to those who are
pregnant, and give birth. We acknowledge that not all people who are pregnant and give birth identify as women, and it is
important that evidence-based care for maternity, perinatal and postnatal health is inclusive.
Funding to conduct this trial was provided by the Chief Scientist Office, Scotland (reference TCS/21/09). The study drug
used in this trial was provided by Anji Pharmaceuticals Inc, USA.REC name
East of England - Cambridge East Research Ethics Committee
REC reference
23/EE/0012
Date of REC Opinion
21 Jun 2023
REC opinion
Further Information Favourable Opinion