Once-Daily vs Twice-Daily Insulin Glargine in Pregestational Diabetes Management

Once-Daily Versus Twice-Daily Insulin Glargine in the Management of Patients With Pregestational Diabetes Requiring Insulin

The purpose of this study is to determine if taking insulin glargine twice a day instead of once a day will better manage pregestational diabetes in pregnant patients. Participants in this study will be randomly assigned to one of two groups: a group that takes insulin glargine once a day, and a group that takes it twice. Continuous glucose monitoring will be used to track blood sugar levels. The main question the study aims to answer is: Will using insulin glargine twice a day instead of once lead to a better glucose time in range?

Study Overview

• Status: Recruiting
• Conditions: Pregnancy; Pregestational Diabetes
• Intervention / Treatment: Drug: Use of insulin glargine once daily; Drug: Use of insulin glargine twice daily

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Marwan Ma'ayeh, MD; Phone Number: 7574467900; Email: maayehmg@odu.edu

Study Locations

• United States
  • Virginia
    • Norfolk, Virginia, United States, 23507
      • Recruiting
      • Sentara Norfolk General Hospital, Norfolk, Virginia 23507
      • Contact: Marwan Ma'ayeh; Phone Number: 7574467900; Email: maayehmg@odu.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients older than 18 years of age;
• The patient is fluent in English, physically and mentally able to understand the informed consent, and is willing to participate in this study;
• Type II diabetes mellitus requiring insulin;
• The patient is between 24 weeks 0 days and 28 weeks 0 days of gestation at the time of enrollment. Gestational age will be determined by last menstrual period, confirmed with a first trimester ultrasound, per the recommended guidelines by the American College of Obstetricians and Gynecologists.
• Currently using or willing to use a clinically indicated continuous glucose monitor for glycemic management

Exclusion Criteria:

• Known allergy or reaction to insulin glargine, or concurrent medical condition where the use of insulin glargine is contraindicated;
• Contraindication to CGM use, patient declines CGM use, or CGM not covered by patient's insurance;
• Known or suspected fetal anomaly or aneuploidy;
• Prisoners;
• Ongoing prenatal care outside EVMS or planned delivery outside Sentara Norfolk General Hospital.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Once-Daily Insulin Glargine; Participants randomized to this arm will take insulin glargine once daily	Drug: Use of insulin glargine once daily; Insulin glargine will be used once daily
Experimental: Twice-Daily Insulin Glargine; Participants randomized to this arm will take insulin glargine twice daily	Drug: Use of insulin glargine twice daily; Insulin glargine will be used twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weekly Time in Range	The mean blood glucose time in range as measured by the continuous glucose monitor	From Day 7 to Day 14 after study enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypertensive disorders of pregnancy	Development of hypertensive disorders of pregnancy	From time of enrollment until time of delivery, up to 20 weeks following enrollment
Preterm birth <34 weeks	Delivery at less than 34 weeks gestation	From time of enrollment to 34 weeks gestation
Preterm birth <37 weeks	Delivery prior to 37 weeks gestation	From time of enrollment until 37 weeks gestation
Spontaneous or Indicated Delivery	Whether delivery was spontaneous or there was an indication for induction or cesarean delivery	From time of enrollment until time of delivery, up to 20 weeks following enrollment
Operative vaginal delivery	Whether an operative vaginal delivery was indicated	From time of enrollment to time of delivery, up to 20 weeks following enrollment
Cesarean Delivery	Whether a cesarean delivery was indicated	From time of enrollment to time of delivery, up to 20 weeks following enrollment
Estimated blood loss	The estimated blood loss during delivery	Duration of labor, up to 24 hours
Quantitative blood loss	The quantified blood loss during delivery	Duration of labor, up to 24 hours
Blood transfusion	Whether a blood transfusion was necessary during or following delivery	From time of enrollment until hospital discharge (up to 42 days post-delivery)
Endometritis	Incidence of endometritis (inflammation of uterine lining)	From time of enrollment to hospital discharge (up to 42 days post-delivery)
Chorioamnionitis	Incidence of chorioamnionitis (placental and amniotic membrane infection)	From time of enrollment until time of hospital discharge (up to 42 days post-delivery)
Wound infection	Infection of wounds left by labor	From time of enrollment to hospital discharge (up to 42 days post-delivery)
Venous thromboembolism	Incidence of venous thromboembolism	From time of enrollment to time of hospital discharge (up to 42 days post-delivery)
Massive transfusion and postpartum hemorrhage	Incidence of massive transfusion and postpartum hemorrhage	From time of enrollment until hospital discharge (up to 42 days post-delivery)
ICU admission	Admission to the ICU	From time of enrollment until hospital discharge (up to 42 days post-delivery)
Maternal death		From time of enrollment to hospital discharge (up to 42 days post-delivery)
Antepartum death	Fetal death	From time of enrollment to time of delivery, up to 20 weeks following enrollment
Intrapartum death	Fetal death during labor and delivery	Duration of labor, up to 24 hours
Neonatal Intubation within 72 hours of birth		From time of delivery to 72 hours later
Continuous positive airway pressure (CPAP) within 72 hours of birth	Use of CPAP for neonate within 72 hours of birth	From time of delivery to 72 hours later
High-flow nasal cannula (HFNC) within 72 hours of birth		From time of delivery to 72 hours later
Cardiopulmonary resuscitation within 72 hours of birth		From time of delivery to 72 hours later
Neonatal Hypoglycemia (glucose <35 mg/dL) requiring IV glucose therapy		From time of delivery to time of hospital discharge, up to 1 year following delivery
Birthweight	Infant birthweight	From time of delivery to time of hospital discharge, up to 1 year following delivery
Neonatal encephalopathy		From time of delivery to time of hospital discharge, up to 1 year following delivery
Seizures	Incidence of neonatal seizures	From time of delivery to time of hospital discharge, up to 1 year following delivery
Shoulder dystocia	Incidence of shoulder dystocia	From time of delivery to time of hospital discharge, up to 1 year following delivery
Birth trauma	Incidence of neonatal birth trauma	From time of delivery to time of hospital discharge, up to 1 year following delivery
Intracranial hemorrhage	Incidence of neonatal intracranial hemorrhage	From time of delivery to time of hospital discharge, up to 1 year following delivery
Hyperbilirubinemia requiring phototherapy or exchange transfusion	Incidence of neonatal hyperbilirubinemia requiring phototherapy or exchange transfusion	From time of delivery to time of hospital discharge, up to 1 year following delivery
NICU admission	Admission of neonate to the neonatal intensive care unit	From time of delivery to time of hospital discharge, up to 1 year following delivery

Collaborators and Investigators

• Sponsor: Eastern Virginia Medical School

Publications and helpful links

General Publications

• American College of Obstetricians and Gynecologists' Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 201: Pregestational Diabetes Mellitus. Obstet Gynecol. 2018 Dec;132(6):e228-e248. doi: 10.1097/AOG.0000000000002960.
• Heinemann L, Linkeschova R, Rave K, Hompesch B, Sedlak M, Heise T. Time-action profile of the long-acting insulin analog insulin glargine (HOE901) in comparison with those of NPH insulin and placebo. Diabetes Care. 2000 May;23(5):644-9. doi: 10.2337/diacare.23.5.644.
• Lepore M, Pampanelli S, Fanelli C, Porcellati F, Bartocci L, Di Vincenzo A, Cordoni C, Costa E, Brunetti P, Bolli GB. Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro. Diabetes. 2000 Dec;49(12):2142-8. doi: 10.2337/diabetes.49.12.2142.
• Ashwell SG, Gebbie J, Home PD. Twice-daily compared with once-daily insulin glargine in people with Type 1 diabetes using meal-time insulin aspart. Diabet Med. 2006 Aug;23(8):879-86. doi: 10.1111/j.1464-5491.2006.01913.x.
• Gabbe SG, Calfas J, Simpson JL, et al. Obstetrics: Normal and Problem Pregnancies. Elsevier; 2017. doi:10.1016/C2013-0-00408-2
• Fishel Bartal M, Ashby Cornthwaite JA, Ghafir D, Ward C, Ortiz G, Louis A, Cornthwaite J, Chauhan SSP, Sibai BM. Time in Range and Pregnancy Outcomes in People with Diabetes Using Continuous Glucose Monitoring. Am J Perinatol. 2023 Apr;40(5):461-466. doi: 10.1055/a-1904-9279. Epub 2022 Jul 20.
• Jethwani P, Saboo B, Jethwani L, Chawla R, Maheshwari A, Agarwal S, Jaggi S. Use of insulin glargine during pregnancy: A review. Diabetes Metab Syndr. 2021 Jan-Feb;15(1):379-384. doi: 10.1016/j.dsx.2021.01.012. Epub 2021 Jan 22.
• Feghali M, Venkataramanan R, Caritis S. Pharmacokinetics of drugs in pregnancy. Semin Perinatol. 2015 Nov;39(7):512-9. doi: 10.1053/j.semperi.2015.08.003.
• Eledrisi M, Suleiman NN, Salameh O, Khair Hamad M, Rabadi O, Mohamed A, Al Adawi R, Salam A. Twice-daily insulin glargine for patients with uncontrolled type 2 diabetes mellitus. J Clin Transl Endocrinol. 2018 Dec 11;15:35-36. doi: 10.1016/j.jcte.2018.12.002. eCollection 2019 Mar. No abstract available.
• Candido R, Wyne K, Romoli E. A Review of Basal-Bolus Therapy Using Insulin Glargine and Insulin Lispro in the Management of Diabetes Mellitus. Diabetes Ther. 2018 Jun;9(3):927-949. doi: 10.1007/s13300-018-0422-4. Epub 2018 Apr 13.
• Westerbacka J, Duverne M, Grulovic N, Thummisetti S, Doder Z. Insulin glargine 300 U/mL safety data in pregnancy. Diabetes Obes Metab. 2025 May;27(5):2322-2325. doi: 10.1111/dom.16295. Epub 2025 Mar 19. No abstract available.

Study record dates

Study Major Dates

• Study Start (Estimated): May 18, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: October 31, 2025
• First Submitted That Met QC Criteria: November 3, 2025
• First Posted (Actual): November 5, 2025

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 13, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: continuous glucose monitoring
• Other Study ID Numbers: 25-09-FB-0214

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No