A Phase 4 interventional study of Metformin and Insulin in Gestational Diabetes Mellitus and Pregnancy, High Risk, sponsored by Ohio State University. Recruiting at 26 sites in United States. Open to female participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-07.
Sponsored by Ohio State University · Phase 4, Interventional, and Treatment
This is a non-inferiority patient-centered and pragmatic comparative-effectiveness pregnancy randomized controlled trial (RCT) with postpartum maternal and child follow-up through 2 years of 1,572 individuals with gestational diabetes mellitus (GDM) randomized to oral metformin versus injectable insulin.
This study will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. A total of 1,572 pregnant individuals with GDM who need pharmacotherapy will be recruited at 20 U.S. sites using consistent treatment criteria to metformin versus insulin. Participants and their children will be followed through delivery to two years postpartum.
Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycemic control decreases the risk of adverse pregnancy outcomes for the pregnant individual with GDM and the infant exposed in utero (1). One in four individuals with GDM will require pharmacotherapy to achieve glycemic control. Insulin has been the mainstay of pharmacotherapy. Metformin is an alternative option increasingly used in clinical practice (2). Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterized, adequately powered, and diverse U.S. population remain lacking (3). Because metformin crosses the placenta, long-term safety data, in particular the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remains to be characterized, including barriers for and facilitators of metformin versus insulin use.
In a two-arm open-label, pragmatic comparative effectiveness randomized controlled trial (RCT), the DECIDE Study will examine whether metformin is not inferior to insulin in reducing adverse pregnancy outcomes and is comparably safe for exposed mothers and children, and whether patient-reported factors, including facilitators of and barriers to use, differ between metformin versus insulin use. The DECIDE Study Consortium will recruit and retain 1,572 pregnant individuals with GDM who need pharmacotherapy at 20 U.S. sites to metformin versus insulin and follow them and their children through delivery and then to 2-years
Primary aim:
To evaluate whether outcomes in pregnant individuals randomized to metformin are not inferior to those in pregnant individuals randomized to insulin for the composite adverse neonatal outcome defined as large-for-gestational-age birthweight (LGA), hypoglycemia, hyperbilirubinemia, or death.
Secondary aims:
842 studies on the registry are indexed under Diabetes, Gestational; 198 are open to participants now.
This study's planned enrollment of 1,572 is above the median of 110 across 550 interventional studies indexed under Diabetes, Gestational.
Browse Diabetes, Gestational studies →Ohio State University is the lead sponsor of 640 studies on the registry; 144 are open to participants now.
Of its 60 completed or terminated interventional studies of FDA-regulated products, 45 (75%) have results posted.
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Exclusion criteria:
Metformin as either immediate- or extended-release formulations can be utilized, and titrated to a maximum daily dose of 2,500 mg. Participants receiving metformin will have insulin added only if they have not achieved euglycemia for at least 30% of glucose values after generally receiving the maximum daily dose of metformin of 2,500 mg, or in select situations in the setting of participant intolerance due to mild gastrointestinal symptoms. Participants will be asked to continue taking metformin after treatment supplementation with insulin.
Drug: Metformin
Insulin will be initiated utilizing clinical standards using trimester-specific weight-based dosing criteria, including both basal and prandial insulins for up to a total of 4 daily injections. Consistent with clinical practice, some people may be managed with a single dose of intermediate- or long-acting insulin at night to treat isolated fasting hyperglycemia, while others may require additional treatment of postprandial hyperglycemia with shorter-acting insulin. The sites' insulin formularies include rapid- (Novolog and Humalog), intermediate- (Humulin N, Novolin N, and NPH), and long-acting insulins (Detemir and Lantus).
Drug: Insulin
Individuals randomized to this arm will receive oral metformin tablets for their Gestational diabetes mellitus treatment.
Individuals randomized to this arm will receive injectable insulin for their Gestational diabetes mellitus treatment.
A neonatal composite adverse outcome of large-for-gestational-age (LGA) birthweight, hypoglycemia, hyperbilirubinemia, and/or death.
LGA will be defined as a birthweight ≥90th%tile for gestational age based on a US birth certificate reference adjusted for parity and/or fetal sex. Neonatal hypoglycemia will be defined as a blood glucose \<35 mg/dL or treatment \<24 hours after birth with either IV, PO, or gel glucose therapy. Neonatal hyperbilirubinemia will be defined as treated with phototherapy or exchange transfusion in the first postnatal week and either treatment in the first postnatal week or kernicterus. Fetal or neonatal death can be due to any indication between randomization to hospital discharge or 30 days postnatal if still hospitalized (excluding voluntary pregnancy termination).
Time frame: LGA at birth. Hypoglycemia <24 hours after birth. Hyperbilirubinemia within the first week after birth. Death between randomization to hospital discharge or 30 days postnatal.
Child body mass index (BMI) at 2 years of age
Child BMI measured in kg/m2 as a continuous measure standardized using U.S. CDC reference adjusted for child sex
Time frame: 2 years of age.
Hypertensive disorder of pregnancy, HDP (maternal)
HDP will include either gestational hypertension or preeclampsia. Gestational hypertension will be defined as: systolic blood pressure of 140 mm Hg or more or diastolic blood pressure of 90 mm Hg or more on two occasions at least 4 hours apart after 20 weeks of gestation in a woman with a previously normal blood pressure. Preeclampsia will be defined as: above blood pressure criteria AND proteinuria (300 mg or more per 24 hour urine collection, protein/creatinine ratio of 0.3 mg/dL or more, or dipstick reading of 2+) OR thrombocytopenia (platelet count less than 100 109/L), renal insufficiency (serum creatinine greater than 1.1 mg/dL or a doubling of the serum creatinine concentration in the absence of other renal disease), impaired liver function (elevated blood concentrations of liver transaminases to twice normal concentration), pulmonary edema, new-onset headache or visual symptoms not attributed to other diagnoses.
Time frame: Randomization to delivery
Gestational weight gain (maternal)
Gestational weight gain between weight at first prenatal visit and weight at delivery based on z-score and defined as excess versus within Institute of Medicine (IOM) recommendations based on first pregnancy BMI.
Time frame: Initiation of prenatal care to delivery
Mode of delivery (maternal)
Cesarean delivery or vaginal delivery
Time frame: At birth
Obstetric perineal/anal sphincter injuries (maternal)
First degree: Injury to perineal skin only; Second degree: Injury to perineum involving perineal muscles but not involving anal sphincter; Third degree: Injury to perineum involving anal sphincter complex, including 3a: Less than 50% of external anal sphincter thickness torn; 3b: More than 50% external anal sphincter thickness torn; and 3c: Both external anal sphincter and internal anal sphincter torn; and Fourth degree: Injury to perineum involving anal sphincter complex (external anal sphincter and internal anal sphincter) and anal epithelium.
Time frame: At birth
Preterm birth (child)
Preterm birth \<37 weeks and \<34 weeks based on project gestational age
Time frame: At birth
Requiring mechanical ventilation (child)
Intubation, continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) for ventilation or cardiopulmonary resuscitation within first 72 hours of birth
Time frame: <72 hours after birth
NICU admission (child)
Admitted to NICU or intermediate nursery ≥72 hours, any indication
Time frame: Birth to delivery discharge.
Oxygen support (child)
Requiring oxygen support
Time frame: <72 hours after birth
Respiratory distress syndrome (child)
Signs of respiratory distress with oxygen requirement and confirmed by chest x-ray.
Time frame: Anytime during the first 72 hours after birth
Body mass index (BMI) (maternal)
Continuous measure, using standardized protocol as kg/m2.
Time frame: 2-year follow-up
Obesity overall and by class (maternal)
BMI per the following classifications: Normal or underweight: \< 25 kg/m2; Overweight: 25 to \< 30 kg/m2; Class 1: 30 to \< 35 kg/m2; Class 2: 35 to \< 40 kg/m2; and Class 3: 40 kg/m2 or greater.
Time frame: 2-year follow-up
Anthropometry (maternal)
Waist circumference, continuous measures in cm
Time frame: 2-year follow-up
Anthropometry (maternal)
Hip circumference, continuous measures in cm
Time frame: 2-year follow-up
Anthropometry (maternal)
Waist - to - hip ratio, continuous measure
Time frame: 2-year follow-up
Adiposity (maternal)
Triceps, subscapular, suprailiac skinfolds, continuous measures in cm
Time frame: 2 year follow-up
Type 2 diabetes (maternal)
A1c \> 6.5% OR fasting plasma glucose \> 126 mg/dL OR OGTT \> 200 mg/dL OR prior diagnosis per patient report
Time frame: 2-year follow-up.
Prediabetes (maternal)
A1c 5.7% to 6.4% OR fasting plasma glucose 100 mg/dl to 125 mg/dL OR OGTT 140 to 199 mg/dL
Time frame: 2-year follow-up.
Hypertension (maternal)
Per American Heart Association criteria as below and/or antihypertensive medication or prior diagnosis per patient report, and defined as: Elevated: Systolic between 120-129 and diastolic less than 80 mm Hg; Stage 1: Systolic between 130-139 or diastolic between 80-89 mm Hg; and Stage 2: Systolic at least 140 or diastolic at least 90 mm Hg.
Time frame: 2-year follow-up.
Cholesterol (maternal)
Fasting state, defined as a continuous measure and dichotomous at the following thresholds for each component: Total cholesterol: \> 200 mg/dL; LDL cholesterol: \> mg/dL; HDL cholesterol: \< 40 mg/dL; Triglycerides: \> 200 mg/dL.
Time frame: 2-year follow-up.
Hemoglobin A1c (maternal)
Continuous measure, percentage.
Time frame: 2-year follow-up.
Overweight (child)
BMI ≥85th%tile for age and sex.
Time frame: 2-year follow-up.
Obesity (child)
BMI ≥95th%tile for age and sex.
Time frame: 2-year follow-up.
Anthropometry (child)
Abdominal circumference; age- and sex-adjusted per WHO z-scores for arm circumference.
Time frame: 2-year follow-up.
Adiposity (child)
Triceps/subscapular skinfold thickness \> 90th%tile for age and sex; individual and sum of measures.
Time frame: 2-year follow-up.
Treatment Satisfaction Questionnaire for Medication (TSQM)
The TSQM (version 1.4) comprises 14 items across four domains focusing on effectiveness (three items), side effects (five items), convenience (three items), and global satisfaction (three items) of the medication over the previous 2-3 weeks. With the exception of item 4 (presence of side effects; yes or no), all items have five or seven responses, scored from one (least satisfied) to five or seven (most satisfied). Item scores are summed to give four domain scores, which are in turn transformed to a scale of 0-100. Item 4 was not included for scoring.
Time frame: 6-weeks postpartum.
Questionnaire on Acceptability of Treatment
A set of 5 questions developed in the Rowan et al. RCT assessing patient adherence, preferences, and experiences with metformin versus insulin for GDM (Rowan et al., NEJM, 2008).
Time frame: 6-weeks postpartum.
Plan to share: Yes — PCORI guidelines for data sharing will be followed, including the release of the Analyzable Data Set. This is the final cleaned and locked data set that contains all the data used in conducting the analyses reported in the PCORI Final Research Report and is de-identified in accordance with the HIPAA Privacy Rule.
Supporting information: Study protocol, Sap, Icf, Csr, Analytic code
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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