Effect of Adding Metformin to Insulin in Uncontrolled Diabetic Patients During the 3rd Trimester of Pregnancy

Study Overview
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Brief Summary
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Background Diabetes mellitus (DM) is a significant contributor to adverse obstetric and perinatal outcome. There is now clear and unequivocal evidence that adverse pregnancy outcomes are strongly linked to maternal hyperglycemia, both in the peri-conception period and throughout gestation. Although strict glycemic control does improve outcomes, there is still a higher rate of complications in women with DM and poorer perinatal outcomes . The incidence of type 2 diabetes is rising worldwide at a remarkable rate IDF When receiving large doses of insulin, patients complain of pain at the site of injection leading to compliance issues and poor glycemic control. This can be explained as when taking large doses of insulin it leads to alter absorption kinetics because very large doses are delivered to one site, resulting in a failure to reduce postprandial hyperglycemia, but with later hypoglycemia once the insulin is absorbed. This poor glycemic control in mothers with diabetes leads to an increased risk of severe respiratory distress syndrome, low Apgar scores, neonatal hypoglycemia and neonatal intensive care unit (NICU) admissions . Infants of mothers with diabetes have high rates of being born large for gestational age (LGA) and macrosomic (>4 or 4.5 kg). Macrosomia is associated with increased rates of perinatal asphyxia, meconium aspiration, hypoglycemia, shoulder dystocia, brachial plexus injury, skeletal injuries, and fetal death . Metformin is among the oldest and most well studied oral anti hyperglycemic agents. Its efficacy has been demonstrated both in the primary prevention of disease and secondary prevention of diabetes-related morbidity and mortality. Because of metformin's proven efficacy, low cost, and minimal side effect profile, it is largely recommended as the first line, initial monotherapy and as part of any combination therapy (included with insulin) for the treatment and prevention of type II diabetes . Metformin produces euglycemia by reducing insulin resistance, improving insulin sensitivity, reducing hepatic gluconeogenesis, and increasing peripheral glucose uptake and utilization.

Detailed Description
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Objectives To determine whether the addition of metformin to a standard regimen of insulin is more effective in glycemic control , fetal and neonatal outcome than conventional insulin alone in uncontrolled diabetic patients during the 3rd trimester of pregnancy.

Official Title
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Effect of Adding Metformin to Insulin in Uncontrolled Diabetic Patients During the 3rd Trimester of Pregnancy on Glycemic Control, Fetal and Neonatal Outcomes ,Randomized Controlled Trial

Conditions
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Diabetes Mellitus Pregnancy

Intervention / Treatment
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* Drug: Metformin
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Diabetic pregnant patients with single living fetus Patients with gestational or type 2 diabetes Patients on insulin in the 3rd trimester of pregnancy HbA1c level between 7% to 11% All patients require a dating ultrasound to confirm gestational age, viability and rule out multiple. Exclusion Criteria: Patients with type 1 diabetes Patients with congestive heart failure or a history of congestive heart failure Patients with renal insufficiency Patients with intolerance or hypersensitivity to metformin Patients having current significant gastrointestinal problems such as severe vomiting requiring intravenous fluids or hospitalization Presence of acute or chronic metabolic acidosis, including diabetic ketoacidosis, a history of diabetic ketoacidosis or history of lactic acidosis Patients with liver impairment Patients with known higher order pregnancies (twins, triplets, etc.) Patients having a known potentially fetal lethal anomaly

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metformin Group<br>will include 75 patients who will be treated with metformin ( 1gm with the 2 main meals ) combined with insulin therapy | Drug: Metformin<br>* 1gm tablet with the 2 main meals<br>Drug: Insulin<br>* subcutaneous insulin daily administration<br>|
| Experimental: Insulin alone group<br>will include 75 patients who will be treated with insulin alone | Drug: Insulin<br>* subcutaneous insulin daily administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal glycemic control 3 months. | blood glucose levels | 3 months | 
| Maternal insulin requirements | Daily Insulin doses requirements | 3 months | 
| Maternal Blood glucose readings | fasting and 2 hours post prandial blood sugar. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maternal weight gain | measured by kilograms | 3 months | 
| weekly fetal weight gain | measured by ultrasound in grams | 3 months | 
| increase of attacks of maternal hypoglycemia. | maternal hypoglycemia defined by plasma glucose level below 65 mg/dl | 3 months | 
| fetal outcomes | intra uterine fetal death (IUFD) | 3 months | 
| Neonatal outcomes | RDS | 1 week |