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

NCT05479214 | Completed Phase 4

• 1 other identifier: reda-metformin
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Mellitus Pregnancy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (5)

• Maternal weight gain

  3 months

• weekly fetal weight gain

  3 months

• increase of attacks of maternal hypoglycemia.

  3 months

• fetal outcomes

  3 months

• Neonatal outcomes

  1 week

Study Arms (2)

Metformin Group

EXPERIMENTAL

will include 75 patients who will be treated with metformin ( 1gm with the 2 main meals ) combined with insulin therapy

Drug: Metformin; Drug: Insulin

Insulin alone group

EXPERIMENTAL

will include 75 patients who will be treated with insulin alone

Drug: Insulin

Interventions

Metformin DRUG

1gm tablet with the 2 main meals

Metformin Group

Insulin DRUG

subcutaneous insulin daily administration

Insulin alone group; Metformin Group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: pregnant women in the 3rd trimester
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Cairo University

Cairo, Egypt

Location

Related Publications (10)

• 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.

  PMID: 24705609 BACKGROUND

• 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.

  PMID: 9203460 BACKGROUND

• 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.

  PMID: 25874236 BACKGROUND

• 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.

  PMID: 27549587 BACKGROUND

• 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.

  PMID: 18297573 BACKGROUND

• 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.

  PMID: 17336651 BACKGROUND

• 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.

  PMID: 24847880 BACKGROUND

• 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.

  PMID: 21843303 BACKGROUND

• 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.

  PMID: 28761217 BACKGROUND

• 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.

  PMID: 28217599 BACKGROUND

MeSH Terms

Conditions

Diabetes, Gestational

Interventions

Metformin; Insulin

Condition Hierarchy (Ancestors)

Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: June 26, 2022
• First Posted: July 29, 2022
• Study Start: July 29, 2022
• Primary Completion: January 1, 2023
• Study Completion: February 10, 2023
• Last Updated: February 21, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

EG (1)