METAFOR: studying delayed-release metformin to control blood sugar levels for women with gestational diabetes

INTERVENTION: ARM 1 (Non‐randomised): Population: 20 pregnant women diagnosed with gestational diabetes with singleton pregnancies and a clinically documented plan to have birth by elective Caesarean section =37 weeks’ gestation. Duration of treatment phase: 24 hours Treatment allocation: On receipt of a trial specific prescription, Pharmacy will dispense 4 Metformin DR 900mg tablets (1 to be taken by participant, 3 provided as an overage). Dose: One Metformin DR 900mg tablet orally within 3 to 8 hours prior to planned Caesarean section Follow Up: Delivery outcomes collected from mother and baby records at 28 days post‐delivery (+/‐ 3 days) ARM 2 (Non‐randomised): Population: 10 pregnant women diagnosed with gestational diabetes with singleton pregnancies between =28+0 and =36+0 weeks gestation. Only patients from the Edinburgh Royal Infirmary, NHS Lothian site will be recruited to this arm of the study. Arm 2 requires a day admission to the Clinical Research Facility Trials Unit and a single dose of metformin DR with serial blood sampling. Duration of treatment phase: 24 hours Treatment allocation: On receipt of a trial specific prescription, Pharmacy will dispense 4 Metformin DR 900mg tablets (1 to be taken by participant, 3 provided as an overage). Dose: One Metformin DR 900 mg tablet to be taken orally with or after breakfast and 1.5 hours (‐1+2 hours) prior to commencement of blood sampling at clinical research facility. Follow Up: Delivery outcomes collected from mother and baby records at 28 days post‐delivery (+/‐ 3 days) ARM 3 (Randomised crossover, web‐based randomis CONDITION: Gestational diabetes in pregnancy ; Pregnancy and Childbirth PRIMARY OUTCOME: Fetal metformin exposure measured by the maternal: fetal serum metformin ratio using paired maternal and umbilical cord blood samples at delivery by elective Caesarean section in Arm 1 up to 3 months following delivery, data extracted from record of mother and baby. SECONDARY OUTCOME: ; Up to 3 months following delivery, data extracted from record of mother and baby:; ; Arm 1:; 1.1. Placental metformin level at delivery; 1.2. Placental metformin transporter levels at delivery; 1.3. Maternal plasma metformin level at delivery; 1.4. Fetal serum metformin level at delivery; 1.5. Fetal arterial:venous metformin ratio at delivery; 1.6. Detection of metformin in maternal serum 24 hrs post‐delivery; ; Arm 2:; 2.1. AUC of maternal serum metformin levels in the third trimester.; 2.2. Pharmacokinetic parameters of metformin in maternal blood, including peak serum concentration, half‐life, bioavailability, renal clearance; 2.3. Metformin concentrations in maternal urine; ; Arm 3:; 3.1. Percentage of eligible participants recruited i.e. number who agree to take part out of all eligible participants who are approached.; 3.2. Side‐effects of treatment by questionnaire; 3.3. Acceptability of treatment by questionnaire; 3.4. Concordance with treatment by questionnaire; 3.5. Percentage maternal blood glucose readings within local clinical target range; 3.6. Need for additional gestational diabetes therapy at the end of 1 week of metformin DR/IR; 3.7. Average plasma glucose concentration; INCLUSION CRITERIA: 1. Women who are pregnant with singleton pregnancy 2. Women with a documented diagnosis of gestational diabetes in their current pregnancy EITHER/OR Women who are documented to be currently treated for gestational diabetes due to a documented history of gestational diabetes in a previous pregnancy 3. Women who are able to give written informed consent to participate In addition: Arm 1: 1. Planned for elective Caesarean section at =37 weeks gestation 2. Women with gestational diabetes documented to be treated with diet alone Arm 2: 1. Women who are in the third trimester of pregnancy (=28+0 weeks and =36+0 weeks gestation at consent) 2. Women with gestational diabetes documented to be treated with diet alone Arm 3: 1. Women =36+0 weeks pregnant at randomisation 2. Women with gestational diabetes documented to be treated with diet and standard metformin IR (stan