Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Randomized Controlled Clinical Trial of Treatment of Mild Gestational Diabetes With Glyburide Versus Placebo
Brief Summary: This is a randomized prospective trial which addresses the question of whether use of an oral hypoglycemic agent as an adjunct to diet therapy in women with mild gestational diabetes will result in achieving euglycemia in a shorter period of time and, in turn, result in less frequent maternal and neonatal morbidities. This study is designed to test the hypothesis that in women with mild GDM, use of Glyburide in addition to diet and nutritional counseling lowers mean infant birth weight by 200 grams as compared with diet and nutritional counseling alone.


Options:
A: 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
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:

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.
D: Inclusion Criteria

1. Pregnancies in women with pre-pregnancy diagnosis of NIDDM (Type 2 DM) and pregnancy continued beyond the first trimester.
2. Women with gestational diabetes mellitus who are at 20-34 weeks of gestation.
3. Women who have glucose elevations consistent with undiagnosed diabetes in pregnancy.
4. Women with impaired glucose tolerance (IGT) at any gestational age of pregnancy and pregnancy continued beyond first trimester.
5. Singleton pregnancy.

Exclusion Criteria:

1. Women who have contraindication for metformin intake.
2. A recognized fetal anomaly at 14-16 weeks ultrasound examination at the time of study entry.
3. Ruptured membranes at time of study entry.
4. Women with IDDM (Type 1 DM) entering pregnancy.
5. Presence of any other medical disorder like essential hypertension, renal disease, hepatic disease, hypothyroidism, cardiac disease.
6. Presence of diabetic complications.
7. Patient already on Sulphonylureas.
8. Multiple pregnancy.
9. Gestational diabetes controlled on diet alone.

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Answer: A