# Metformin Impact on Maternal and Infant Cardiometabolic Health (MIMICH), an open-label randomised controlled trial, and Metformin Impact on Maternal and Cardiometabolic Health After Pregnancy (MIMICH II)

## TL;DR

This study investigates how metformin affects maternal and infant health during and after high-risk pregnancies, focusing on placental function and fetal growth.

## Contribution

The study introduces a novel approach to assess metformin's impact on placental disease and fetal growth using longitudinal biometric measurements.

## Key findings

- The study will evaluate metformin's effect on fetal growth trajectory using longitudinal ultrasound measurements.
- MIMICH II will assess maternal and infant cardiometabolic health post-pregnancy through follow-up measurements.
- The trial addresses limitations of using birthweight alone by incorporating third-trimester growth deviations.

## Abstract

Whilst women with diabetes are at risk of having a pregnancy complicated by foetal macrosomia, a small but important minority of women develop placental dysfunction leading to a small for gestational age infant (SGA < 10th centile) (20%) and/or the development of pre-eclampsia (12–18%) which may in some cases require preterm birth. In the UK, currently, metformin is offered as first line to treat diabetes during pregnancy, regardless of the risk of placental disease; however, the effect of metformin on placental function and foetal growth remains unclear. Metformin Impact on Maternal and Infant Cardiometabolic Health (MIMICH) and Metformin Impact on Maternal and Infant Cardiometabolic Health After Pregnancy (MIMICH II) aim to better understand the impact of metformin in the context of pregnancies at high risk of placental disease by evaluating the effect of metformin on foetal growth, placental function and maternal and infant cardiometabolic health.

MIMICH is a randomised control trial (RCT) comparing routine treatment for diabetes, the standard of care, to withholding metformin (the intervention) during pregnancy, in women with type 2 diabetes or gestational diabetes (GDM) who have maternal or uteroplacental risk factors for placental disease in a target sample of 225 participants. Participants receive the recommended schedule of antenatal care, including serial biometry ultrasound with the addition of fractional thigh volume measurement. The primary outcome will be change in estimated weight z-score from second trimester to birth. The MIMICH II study will follow up the mothers and infants at 3–6 months and 12–15 months after pregnancy. Study procedures include anthropometric measurements from both mother and baby, data collection about medications, complications after birth and feeding, and maternal blood sampling. Infant echocardiography, blood pressure measurements and venepuncture will also be undertaken where possible.

Previous studies investigating hypoglycaemic agents in pregnancy have used birthweight as the primary outcome. In pregnancies where there are conflicting exposures influencing foetal growth and placental function (e.g. hypertension and hyperglycaemia), absolute birthweight is not sufficient to detect subtle, but clinically significant changes in foetal growth and placental function. To address this limitation, longitudinal measures of foetal growth will be used to quantify the deviation in foetal growth trajectory in the third trimester, using comparison with foetal growth prediction based on second trimester biometry from the same foetus.

ISRCTN13866189. Registered on February 15, 2021.

The online version contains supplementary material available at 10.1186/s13063-025-09154-5.