Metformin Use to Improve Pregnancy Outcome in Women With Type 1 Diabetes.
- Conditions
- Diabetic PregnancyType1diabetesInsulin Resistance
- Interventions
- Drug: Placebo Oral TabletDrug: metforminhydrochloride
- Registration Number
- NCT03765359
- Lead Sponsor
- Tampere University Hospital
- Brief Summary
The study investigates whether additional metformin medication in combination with regular insulin treatment will decrease the need of insulin for women with diabetes mellitus type 1 during pregnancy.
- Detailed Description
Insulin resistance during pregnancy of diabetes mellitus type 1 patients (DM1) increases the need for insulin and makes it more difficult to maintain normoglycemia. Fetal exposure to hyperglycemia induces macrosomia which increases fetal and neonatal morbidity and mortality. Further more obesity and excess weight gain during pregnancy enhances insulin resistance and it's an independent risk factor for fetal macrosomia.
Metformin is a medical treatment for type 2 diabetes (DM2) where consequential pathophysiology includes insulin resistance. It reduces hepatic glucose production and enhances the use of glucose in muscles relieving insulin resistance. Metformin has also found to inhibit weight gain effectively.
Metformin has approved to be safe and effective in patients with gestational diabetes (GDM). It has found to reduce weight gain and improve postprandial blood glucose levels during pregnancy and reduce neonatal birth trauma in GDM. However, there are no previous studies about the use of metformin in pregnant women with DM1.
Two hundred women with DM1 will be randomized to get placebo or metformin in addition to regular insulin treatment. The sample size has been estimated to demonstrate the difference of 15 % in the need to increase insulin dosages during the pregnancy between the study groups.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 101
- a pregnancy of a woman with type 1 diabetes.
- multiple pregnancy, significant underlying disease (hearth disease, kidney transplant, IBD (inflammatory bowel disease ), SLE (systemic lupus erythematosus ), diseases with use of high dosage corticosteroids (severe asthma or rheumatic disease), severe complications of diabetes (nephropathy, neuropathy, gastroparesis or severe retinopathy), substance abuse, smoking, BMI <18, strong early pregnancy nausea (=hyperemesis)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Oral Tablet Placebo Oral Tablet Placebo tablets starts on 12-14 weeks of gestation. The starting dosage is 1 tablet x1 and it is increased gradually 1 tablet a week up to 2+2 tablets daily. Duration of the treatment is approximately until one week before delivery. Otherwise placebo treatment combined with regular insulin and follow-up during pregnancy follows the national guidelines. metforminhydrochloride metforminhydrochloride Metformin medication starts on 12-14 weeks of gestation. The starting dosage is 1 tablet (500 mg) x1 and it is increased gradually 1 tablet a week up to 2+2 tablets (2000mg) daily. Duration of the treatment is approximately until one week before delivery. Otherwise metformin treatment combined with regular insulin and follow-up during pregnancy follows the national guidelines.
- Primary Outcome Measures
Name Time Method Changes in the insulin need during pregnancy from 5-10 gestational weeks until the delivery The insulin dosage (IU/ml) in two weeks sets
- Secondary Outcome Measures
Name Time Method Pregnancy complications 22-40 weeks of gestation incidence of intrauterine death (intrauterine death after 22 weeks of gestation or fetal weigth over 500g) (%)
Newborn outcome After the delivery Acidosis of the newborn (pH)
Thigh fractional volume ultrasound from gestational weeks 20 until delivery Fetal weight estimation (g) is specified by thigh fractional volume ultrasound program
Blood glucose balance during pregnancy HbA1c from gestational weeks 5 until the delivery HbA1c (mmol/mol)
Change in the weight from gestational weeks 5 until the delivery Weight gain (g) during pregnancy
Rate of the operative vaginal deliveries The delivery Rate of the operative vaginal deliveries (%)
Newborn variables (gestational age) After the delivery Rate of the premature deliveries (=deliveries before 37 weeks of gestation) (%)
Incidence hepatogestosis from gestational weeks 20 until the delivery Incidence hepatogestosis (%)
macrosomia from gestational weeks 20 until the delivery estimated fetal weight in ultrasound (grams)
Rate of the caesarean sections The delivery Rate of the caesarean sections (%)
Rate of the shoulder dystocia The delivery Rate of the shoulder dystocia (%)
Rate of the perineal tears The delivery Rate of the perineal tears (%)
Newborn variables After the delivery weight of the newborn (g)
Blood glucose balance during pregnancy AVG, SD, CV from gestational weeks 5 until the delivery mean blood glucose (mmol/l) level, standard deviation (SD) and the coefficient of variation of the blood glucose levels
Labour The delivery rate of spontaneous delivery (%)
Postpartum bleeding The delivery postpartum bleeding (ml)
Cost benefit calculations (hospitalization) 14-40 weeks of gestation The need of hospitalization during pregnancy (days/pregnancy)
Incidence of pre-eclampsia from gestational weeks 20 until the delivery Incidence of pre-eclampsia (%)
Change in the blood pressure from gestational weeks 5 until the delivery Blood pressure (mmHg)
Labor complications The delivery rate of induced delivery (%)
Newborn outcome (hypoglycemia) After the delivery The occurrence of hypoglycemia (=plasma glucose under 2.6mmol/l or usage of iv glucose infusion) (%)
Cost benefit calculations (all policlinical controls of the child) Until the age of one year The need of policlinical controls of the child (number of visits)
high sensitive-CRP 7-10, 26-28 and 34-36 weeks of gestation high sensitive-CRP (mg/l)
Newborn outcome (intensive care) After the delivery The need of NICU (neonatal intensive care unit) treatment (days)
Newborn outcome (Erb's) After the delivery Incidence of the Erb's paresis (%)
Cost benefit calculations (sick leaves) from gestational weeks 12 until delivery The need of sick leaves during pregnancy (days)
Cost benefit calculations (visits to maternity outpatient clinic or internal medicine policlinic) 14-40 weeks of gestation The need of polyclinical controls during pregnancy (number of visits/pregnancy)
Cost benefit calculations (all outpatient visits after delivery ) One year after the delivery The need of policlinical controls of the diabetic mother after the delivery (number of visits)
Cost benefit calculations (hospitalization after delivery, all departments) Up to one year after the delivery The need of hospitalization of the diabetic mother after the delivery (days)
lipids 7-10, 26-28 and 34-36 weeks of gestation cholesterol, high density lipoprotein, low density lipoprotein, triglyserids (mmol/l)
Cost benefit calculations (all hospitalization of the child) Until the age of one year The need of hospitalization of the child (days)
Inflammatory markers 7-10, 26-28 and 34-36 weeks of gestation adiponectin, leptin, resistin, IL-6, TNF-α (pg/ml)
Trial Locations
- Locations (5)
Helsinki University Hospital
🇫🇮Helsinki, Finland
Turku University Hospital
🇫🇮Turku, Finland
Tampere University Hospital
🇫🇮Tampere, Finland
Oulu University hospital
🇫🇮Oulu, Finland
Central Finland Health Care District
🇫🇮Jyväskylä, Finland