Comparator Trial Using Insulin Glulisine vs. Insulin Lispro for Treatment of Gestational Diabetes

• Serum blood glucose area under the curve (AUC) at one 4-hour in-clinic meal challenge [ Time Frame: week 2 of insulin treatment ] [ Designated as safety issue: No ]
  patients will come to the study site under fasting conditions and eat a standardized meal in the morning post administration of insulin NPH and their randomized bolus insulin.
• Compare A1C at enrollment and weekly until delivery [ Time Frame: up to 36 weeks ] [ Designated as safety issue: No ]
  A1C is measured weekly at each pregnancy visit up to 26 visits. Subjects are enrolled at 20-32 weeks gestation and have weekly visits to obtain A1C through delivery, and again at the 6-week postpartum visit.
• Compare incidence of hypoglycemic episodes <60 mg/dL with symptoms [ Time Frame: up to 36 weeks ] [ Designated as safety issue: Yes ]
  Hypoglycemic episodes since the last visit will be reported at each pregnancy visit, usually weekly, from enrollment at 10-30 weeks gestation through delivery and at the 6-week postpartum visit if continuing to take insulin.

• Serum blood glucose area under the curve (AUC) at one 4-hour in-clinic meal challenge [ Time Frame: week 2 of insulin treatment ] [ Designated as safety issue: No ]
  patients will come to the study site under fasting conditions and eat a standardized meal in the morning post administration of insulin NPH and their randomized bolus insulin.
• Compare A1C at enrollment and weekly until delivery [ Time Frame: up to 36 weeks ] [ Designated as safety issue: No ]
  A1C is measured at each pregnancy visit, usually weekly, from enrollment at 10-30 weeks gestation through delivery, and again at the 6-week postpartum visit.
• Compare incidence of hypoglycemic episodes <60 mg/dL with symptoms [ Time Frame: up to 36 weeks ] [ Designated as safety issue: Yes ]
  Hypoglycemic episodes since the last visit will be reported at each pregnancy visit, usually weekly, from enrollment at 10-30 weeks gestation through delivery and at the 6-week postpartum visit if continuing to take insulin.

• Compare incidence of birth weight >90th percentile [ Time Frame: delivery ] [ Designated as safety issue: No ]
• Compare incidence of primary cesarean section [ Time Frame: delivery ] [ Designated as safety issue: No ]

We hypothesize that insulin glulisine is non-inferior to currently proven rapid-acting insulin lispro when used in a basal/bolus regimen to treat hyperglycemia in patients with gestational diabetes mellitus.

To date, only two rapid-acting insulin analogs have been shown to be safe and effective for the treatment of diabetes during pregnancy: insulin aspart and insulin lispro.

The pharmacokinetics and pharmacodynamics of insulin glulisine are unique and insulin glulisine may be the best rapid-acting analog for the treatment of post-prandial hyperglycemia. We believe that insulin glulisine should be evaluated in women with gestational diabetes for its potential efficacy.

• Drug: NPH
  Long acting insulin NPH dosing will be titrated weekly derived from the patients current weight and gestational age
  Other Name: Humulin N, Novolin N
• Drug: Insulin LISPRO
  Insulin lispro dosing will be titrated weekly based on the patient's average SMBG readings from each meal during the past three days
  Other Name: Humalog
• Drug: Insulin glulisine
  Insulin glulisine will be titrated weekly based on the patient's average SMBG readings from each meal during the past three days
  Other Name: Apidra

• Active Comparator: NPH and insulin lispro
  Patients diagnosed with diabetes during pregnancy will be randomized to long acting insulin NPH and short acting insulin lispro in a basal bolus regimen to treat post prandial hyperglycemia using a dosing schedule of 50% NPH calculated by the patients weight and gestational age and 50% lispro pending their last three SMPG average.
  Interventions:

  • Drug: NPH
  • Drug: Insulin LISPRO
• Active Comparator: NPH and insulin glulisine
  Patients with a diagnosis of diabetes during pregnancy will be randomized to using long acting insulin NPH and short acting insulin glulisine as treatment for post prandial hyperglycemia with a 50% NPH dosing schedule based on the weight and gestational age and 50% glulisine schedule based on their last three SMBG result average.
  Interventions:

  • Drug: NPH
  • Drug: Insulin glulisine

Inclusion Criteria:

• Informed Consent to participate in clinical trial
• Pregnant and 20-30 weeks gestation
• Diagnosed with gestational diabetes
• Failed diet therapy (failed lifestyle modification will be defined as 10% or greater SMBG values above pre-meal <90mg/dL and post prandial < 120mg/dL
• Eat at least 2 meals per day

Exclusion Criteria:

• Pregnant women <18 years old
• Blood pressure > 140/80 mmHg
• A1C equal to or greater than 6.5% at time of enrollment
• Pre-pregnancy BMI > 40Kg/m squared
• Evidence of any fetal anomaly on any fetal ultrasound
• Currently using hypoglycemic agent
• Refusal to use insulin before meals
• Inability to understand instructions or to consent to participate
• Pregnant women with history of T1DM or T2DM
• Clinical judgment by investigator that patient is inappropriate for clinical trial or has a metabolic disorder that could interfere with results