Effect of Adding Metformin to Insulin Therapy on Pregnancy Outcomes in Women With Uncontrolled Type I Diabetes.

Effect of Adding Metformin to Insulin Therapy in Pregnant Women With Type I Diabetes as Regards Pregnancy Outcome

A randomized controlled clinical trial will be conducted in KasrELAiny hospitals, Cairo University and Beni-Suef University Hospital, including 80 uncontrolled diabetic pregnant women (type I) in the 3rd trimester (28-32 weeks of pregnancy) divided equally into study group and control group, to compare the usage of both metformin and insulin instead of using insulin alone. Group assignment will be randomized by computer program.

Study Overview

• Status: Completed
• Conditions: Type1 Diabetes Mellitus
• Intervention / Treatment: Drug: Metformin; Drug: Insulin

Detailed Description

A total of 80 uncontrolled diabetic pregnant patients in the 3rd trimester seeking medical advice in Beni-Suef University Hospital and meet the eligibility criteria, are approached about participation in the trial and given information pamphlets describing the study. The patients are asked to sign a consent form and will be assigned to one of the 2 groups: Group A (study group); will include 40 patients who will be treated with metformin

(1 gm twice daily (with the 2 main meals)), combined with insulin therapy Group B (control group); will include 40 patients who will be treated with insulin alone. (Insulin dosage will be adjusted according to endocrinological recommendations) All patients will be managed according to NICE guidelines for diabetes with pregnancy (2015) Maternal assessment

• Full history taking Baseline medical history is obtained along with other baseline demographics and concomitant medications including insulin regimen and dose.
• Thorough clinical examination Maternal weight, height and blood pressure measured and recorded.

• Laboratory investigations;

  • Routine labs: CBC, coagulation profile, liver and kidney function at time of participation, 28-32 weeks of gestation especially renal parameter serum Creatinine.
  • HbA1c at time of 1st examination.
  • FBS, 2h post prandial blood sugar will be done weekly from time of participation till time of delivery
• Fundus examination for early detection of retinal affection at Ophthalmology clinic

Follow up:

1. Fetal weight gain weekly
2. Maternal weight gain weekly

Accordingly:

1. Uncontrolled cases will follow up weekly in the High Risk Pregnancy outpatient clinic until 36 weeks and then admitted to High risk pregnancy department for termination of pregnancy

   o Fetal surveillance will be done by ;CTG weekly, Ultrasound weekly and Fetal kick count daily

2. Resistant uncontrolled cases will be admitted to high risk pregnancy department where capillary blood sugar will be measured 7 times daily Fetal surveillance will be done by ; CTG Daily, Ultrasound every 3 days and Fetal kick count daily

Assessment of Patients at time of termination by:

1. Fasting blood sugar , 2 hours post prandial blood sugar and HBA1C
2. Routine preoperative labs. CBC, coagulation profile, liver and kidney function
3. Fetal weight
4. Maternal weight Neonatal assessment after delivery include the following; APGAR score, neonatal weight, incidence of transient tachypnea of newborn (TTN), acute respiratory distress syndrome (ARDS), neonatal hypoglycemia and NICU admission.

• Study Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 4

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Beniswef university hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Diabetic pregnant patients with type one diabetes and no other chronic disorders
• Patients on insulin in the 3rd trimester of pregnancy (on insulin therapy since start of gestation)
• Patients pregnant in single living fetus with no apparent congenital anomalies
• Haemoglobin A 1 C (HbA1c) level between 7% to 11%
• All patients have done a dating ultrasound to confirm gestational age, viability and rule out any abnormality

Exclusion Criteria:

• Patients with type 2 or gestational diabetes
• Patients with intolerance or hypersensitivity to metformin
• Patients with congestive heart failure or a history of congestive heart failure
• Patients with renal insufficiency
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: combined metformin and insulin	Drug: Metformin; 40 patients will be treated with metformin (1 gm twice daily (with the 2 main meals)), combined with insulin therapy; Drug: Insulin; 40 patients will be treated with insulin alone. (Insulin dosage will be adjusted according to endocrinological recommendations)
OTHER: Insulin only	Drug: Insulin; 40 patients will be treated with insulin alone. (Insulin dosage will be adjusted according to endocrinological recommendations)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HbA1c	the change in level of glycosylated haemoglobin	12 weeks
capillary glucose	the change in level of glucose in capillary blood	12 weeks
fasting blood sugar measurement.	the change in level of glucose in venous blood after fasting for 8 hours	12 weeks
2 hours post prandial blood sugar measurement.	the change in level of glucose in venous blood 2 hours after meal	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maternal weight gain	the change in mothers' weight in kilograms	12 weeks
weekly fetal weight gain measured by ultrasound	the change of fetal weight measured by ultrasound	12 weeks
insulin requirements	the change in dose of insulin taken by patient	12 weeks
attacks of maternal hypoglycemia	Number of patients with plasma glucose level below 65 mg/dl	12 weeks
intra uterine fetal death (IUFD)	The number of patients with death of fetus after 20 weeks of gestation	12 weeks
neonatal weight	The change in neonatal weight in kilograms	12 weeks
preterm birth	The number of patients giving birth berfore 37 completed weeks	12 weeks
neonatal respiratory distress	the number of neonates with neonatal respiratory distress	12 weeks
neonatal hypoglycemia	the number of neonates with plasma glucose level below less than 45 mg/dL (2.5 mmol/L)	12 weeks
neonatal Intensive care admission	the number of neonates with neonatal Intensive care admission	12 weeks

Collaborators and Investigators

• Sponsor: Kasr El Aini Hospital
• Collaborators: Amal Kotb Abdallah; Amir Gabr; Mohamed Abdeltawwab Mahmoud
• Investigators: Principal Investigator: Amal kotb, Beniswef university hospital; Principal Investigator: Amir Gabr, Cairo university kasrelainy hospitals

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 29, 2019
• Primary Completion (ACTUAL): March 29, 2020
• Study Completion (ACTUAL): March 29, 2020

Study Registration Dates

• First Submitted: April 20, 2019
• First Submitted That Met QC Criteria: April 23, 2019
• First Posted (ACTUAL): April 26, 2019

Study Record Updates

• Last Update Posted (ACTUAL): May 28, 2020
• Last Update Submitted That Met QC Criteria: May 26, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: FMBSUREC/05032019/Abd Alaziz

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No