Please select the eligibility criteria that correspond to the clinical trial below.
Title: Pilot Study of Metformin vs. Insulin in Pregnant Overt Diabetics (MIPOD)
Brief Summary: Many women come into pregnancy with diabetes that is controlled with either Metformin or diet control; however, the current standard of care for the treatment of preexisting diabetes in pregnancy is insulin. Metformin is widely used in the non-pregnant population for glycemic control, and has been used in pregnancy for other indications without adverse maternal or fetal outcomes. What remains unproven is the ability of Metformin to adequately control glucose in women during pregnancy.

Our goal is to randomize 100 women who enter pregnancy with diabetes that is controlled by either diet or an oral agent and women who are found to have an abnormal glucose challenge test at less than 20 weeks to either standard treatment with weight based Regular and neutral protamine Hagedorn (NPH) insulin or Metformin. Our hypothesis is that Metformin will provide glycemic control that is equivalent to insulin in these women.


Options:
A: Inclusion Criteria:

1. Women who are between of 18-45 years of age.
2. (i). Women diagnosed with type 2 diabetes prior to pregnancy, OR (ii). Women with undiagnosed type 2 diabetes diagnosed prior to 20 weeks gestation, defined as women presenting with gestational diabetes before 20 weeks gestation with various combinations, as per Canadian Diabetes Association, including:

   * 2 fasting glucose ≥ 7.0 mmol/L, or
   * 2 HbA1c of ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the Diabetes Control and Complications Trial (DCCT) assay, or
   * 1 fasting glucose ≥7.0 mmol/L and 1 HbA1c ≥ 0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay, or
   * 1 fasting glucose ≥ 7.0 mmol/L and 1 two hour (2 hr) ≥ 11.1 on a 75 g Oral Glucose Tolerance Test (OGTT), or
   * 1 HbA1C ≥0.065 (6.5%) performed in a laboratory using a method that is standardized to the DCCT assay and 1 two hour (2 hr) ≥ 11.1 on a 75 g OGTT.
3. Pregnancy gestation between 6+0-22+6 weeks.
4. Live singleton fetus.

Exclusion Criteria:

1. Women who are not on insulin. Women who are on oral hypoglycemic agents will be taken off at the start of the trial and started on insulin prior to randomization.
2. Diabetes diagnosed after 20 weeks gestation.
3. Type 1 diabetes.
4. Known intolerance to metformin.
5. Contraindications to metformin use which include:

(i). Renal insufficiency (defined as serum creatinine of greater than 130 µmol/L or creatinine clearance \<60 ml/min) , (ii). Moderate to severe liver dysfunction (defined as liver enzymes (aspartate aminotransferase (AST) and alanine aminotransferase (ALT)) greater than 3 times the upper limit of normal), (iii). Shock or sepsis, and (iv.) Previous hypersensitivity to metformin.

f. Women with significant gastrointestinal problems such as severe vomiting requiring IV fluids or hospitalization, or active Crohn's or colitis.

g. Previous participation in the trial. h. Women who have a fetus with a known potentially lethal anomaly will be excluded. Information regarding congenital anomalies diagnosed after randomization will be recorded.

i. Known higher order pregnancies (twins, triplets, etc). These women will be excluded as they have a higher rate of adverse outcomes and we want to avoid any inequalities if they are unequally distributed between the groups.

j. Presence of acute or chronic metabolic acidosis, including diabetic ketoacidosis.

k. History of diabetic ketoacidosis or history of lactic acidosis. l. Presence of excessive alcohol intake, acute or chronic. m. Presence of congestive heart failure or history of congestive heart failure.
B: Inclusion Criteria:

* Pregnant
* Gestational age at enrollment 24 - 31 weeks

Exclusion Criteria:

* Diabetes diagnosed prior to pregnancy
* Abnormal gestational diabetes (\>= 135 mg/dl) testing prior to 24 weeks' gestation
* Gestational diabetes in a previous pregnancy
* History of stillbirth or fetal death
* Pregnancy with more than one fetus
* Known major fetal anomaly
* Current or planned corticosteroid therapy
* Asthma requiring medication
* Current or planned beta adrenergic therapy
* Chronic hypertension requiring medication within 6 months of or during pregnancy
* Chronic medical conditions such as HIV/AIDS, kidney disease, or congenital heart disease
* Hematologic or autoimmune disease such as sickle cell disease, other hemoglobinopathies, lupus, or antiphospholipid syndrome
* Maternal or fetal conditions likely to require preterm delivery, such as pre-eclampsia, preterm labor, or intrauterine growth retardation
* Previous or planned tocolytic therapy to induce labor or increase contraction strength
C: Inclusion Criteria:

* Receiving prenatal care at University of North Carolina (UNC), Chapel Hill Obstetric clinics and planning delivery at UNC Women's Hospital
* Diagnosis of Diabetes prior to pregnancy with use of an oral hypoglycemic agent or dietary control
* Diagnosis of early gestational diabetes prior to 20 weeks gestation via abnormal 3 hour glucose challenge testing using the national diabetes data group (NDDG)criteria
* Less than 24 weeks at study enrollment
* Singleton or twin pregnancy
* English or Spanish speaking
* Able to give informed consent

Exclusion Criteria:

* End organ complications of diabetes (retinopathy, renal insufficiency, etc.)
* Prior need for insulin for glycemic control
* History of diabetic ketoacidosis (DKA) or hyperosmolar state
* Prior adverse reaction (ie. lactic acidosis) or allergy to Metformin
* Kidney or liver disease
* Significant medical co-morbidities (lupus, cystic fibrosis, etc.) Hypertension controlled on one medication, well controlled asthma, and well controlled thyroid disease are not excluded.
D: Inclusion Criteria:

* A glucose value of ≥140 mg/dl on a 50-gram oral glucose loading test by plasma at gestational age between 24 weeks 0 days and 27 weeks 6 days based on clinical information
* An Abnormal 3-hour oral glucose tolerance test with a fasting glucose of ≤105 mg/dl
* Gestational age of less than or equal to 28 weeks and 0 days at the time of consent/randomization
* Singleton gestation

Exclusion Criteria:

* Established pregestational diabetes
* Abnormal gestational diabetes testing (≥140) prior to 24 weeks 0 days of gestation. Women who have a negative glucose loading test (\<140mg/dl) before 24 weeks may still be considered for this study if they present again for glucose tolerance testing between 24 and 27 weeks.
* Multiple gestations
* Known major fetal anomaly or fetal demise
* Any renal disease with serum creatinine of \>1.0
* Known liver disease such as hepatitis
* Maternal or fetal conditions likely to require imminent or very preterm delivery such as preeclampsia, preterm premature rupture of the membranes, preterm labor, and intrauterine fetal growth restriction
* Known hypersensitivity or allergic reaction to Glyburide

Answer: C