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

Diabetes Mellitus Pregnancy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05479214
• Other study ID #: reda-metformin
• Status: Completed
• Phase: Phase 4
• Start date: July 29, 2022
• Est. completion date: February 10, 2023

Study information

• Verified date: February 2023
• Source: Cairo University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: February 10, 2023
• Est. primary completion date: January 1, 2023
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus Pregnancy
• Pregnancy in Diabetics

Intervention

Drug:
• Metformin
1gm tablet with the 2 main meals
• Insulin
subcutaneous insulin daily administration

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (1)

Lead Sponsor	Collaborator
Cairo University

Country where clinical trial is conducted

Egypt, 

References & Publications (10)

Ainuddin JA, Karim N, Zaheer S, Ali SS, Hasan AA. Metformin treatment in type 2 diabetes in pregnancy: an active controlled, parallel-group, randomized, open label study in patients with type 2 diabetes in pregnancy. J Diabetes Res. 2015;2015:325851. doi: 10.1155/2015/325851. Epub 2015 Mar 22. — View Citation

Feig DS, Hwee J, Shah BR, Booth GL, Bierman AS, Lipscombe LL. Trends in incidence of diabetes in pregnancy and serious perinatal outcomes: a large, population-based study in Ontario, Canada, 1996-2010. Diabetes Care. 2014 Jun;37(6):1590-6. doi: 10.2337/dc13-2717. Epub 2014 Apr 4. — View Citation

Gibbons A, Flatley C, Kumar S. Cerebroplacental ratio in pregnancies complicated by gestational diabetes mellitus. Ultrasound Obstet Gynecol. 2017 Aug;50(2):200-206. doi: 10.1002/uog.17242. — View Citation

Langer O. Type 2 diabetes in pregnancy: exposing deceptive appearances. J Matern Fetal Neonatal Med. 2008 Mar;21(3):181-9. doi: 10.1080/14767050801929497. — View Citation

Lipscombe LL, Hux JE. Trends in diabetes prevalence, incidence, and mortality in Ontario, Canada 1995-2005: a population-based study. Lancet. 2007 Mar 3;369(9563):750-756. doi: 10.1016/S0140-6736(07)60361-4. — View Citation

Madiraju AK, Erion DM, Rahimi Y, Zhang XM, Braddock DT, Albright RA, Prigaro BJ, Wood JL, Bhanot S, MacDonald MJ, Jurczak MJ, Camporez JP, Lee HY, Cline GW, Samuel VT, Kibbey RG, Shulman GI. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014 Jun 26;510(7506):542-6. doi: 10.1038/nature13270. Epub 2014 May 21. — View Citation

Murphy HR, Steel SA, Roland JM, Morris D, Ball V, Campbell PJ, Temple RC; East Anglia Study Group for Improving Pregnancy Outcomes in Women with Diabetes (EASIPOD). Obstetric and perinatal outcomes in pregnancies complicated by Type 1 and Type 2 diabetes: influences of glycaemic control, obesity and social disadvantage. Diabet Med. 2011 Sep;28(9):1060-7. doi: 10.1111/j.1464-5491.2011.03333.x. — View Citation

Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997 Jul;20(7):1183-97. doi: 10.2337/diacare.20.7.1183. No abstract available. — View Citation

Salber GJ, Wang YB, Lynch JT, Pasquale KM, Rajan TV, Stevens RG, Grady JJ, Kenny AM. Metformin Use in Practice: Compliance With Guidelines for Patients With Diabetes and Preserved Renal Function. Clin Diabetes. 2017 Jul;35(3):154-161. doi: 10.2337/cd15-0045. — View Citation

Shobha P, Mathen S, Abraham J. Glycosylated hemoglobin values in nondiabetic pregnant women in the third trimester and adverse fetal outcomes: An observational study. J Family Med Prim Care. 2016 Jul-Sep;5(3):646-651. doi: 10.4103/2249-4863.197313. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Maternal glycemic control 3 months.	blood glucose levels	3 months
Primary	Maternal insulin requirements	Daily Insulin doses requirements	3 months
Primary	Maternal Blood glucose readings	fasting and 2 hours post prandial blood sugar.	3 months
Secondary	Maternal weight gain	measured by kilograms	3 months
Secondary	weekly fetal weight gain	measured by ultrasound in grams	3 months
Secondary	increase of attacks of maternal hypoglycemia.	maternal hypoglycemia defined by plasma glucose level below 65 mg/dl	3 months
Secondary	fetal outcomes	intra uterine fetal death (IUFD)	3 months
Secondary	Neonatal outcomes	RDS	1 week