Strict Versus Permissive Thresholds for Initiation of Pharmacotherapy in Gestational Diabetes (START 2)

Official title

Strict Versus Permissive Threshold for Initiation of Pharmacotherapy in Gestational Diabetes Mellitus (GDM) With Continuous Glucose Monitoring Use - A Randomized Control Trial (START 2 Trial)

Overview

The aim of our study is to compare neonatal and maternal outcomes using different thresholds for the initiation and titration of pharmacotherapy for gestational diabetes (GDM). Our goal is to compare a Strict and permissive threshold. The Strict study arm target range will be 65-120 mg/dL, with time in range goal of 70%. The permissive study arm target range will be 65-140 mg/dL, with target time in range goal of 70%.

Detailed description

Pregnancy is a state of insulin resistance to ensure that the growing fetus has ample nutrition. Gestational Diabetes (GDM) develops in pregnant patients with pancreatic dysfunction that leads to impairment of glucose tolerance.

Various studies have examined the benefit of treatment for GDM, including the 2005 Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) and the 2009 Landon et al randomized controlled trials. These studies found that treatment was associated with a significant reduction in newborn complications of perinatal death, shoulder dystocia, large for gestational age infants, cesarean delivery, and birth trauma. The specific threshold value for initiation and up-titration of medical therapy is unknown. Lack of evidence leads to a wide variation in clinical practice of pharmacological initiation and titration for GDM. A systematic review and meta-analysis by Caissutti in 2019 analyzed criteria for initiating pharmacotherapy for GDM and noted the following: 12 of 15 trials initiated pharmacotherapy after 1-2 abnormal values over 1-2 weeks, 2 studies initiated pharmacotherapy after 50% of overall values were abnormal, and 1 study initiated pharmacotherapy after 30% of overall values were abnormal. However, there have been no randomized controlled trials of head-to-head comparison of different thresholds.

The aim of our study is to compare neonatal and maternal outcomes using different thresholds for the initiation and titration of pharmacotherapy for GDM using continuous glucose monitor. Our goal is to compare a Strict and permissive threshold. The Strict study arm target range will be 65-120 mg/dL, with time in range goal of 70%. The permissive study arm target range will be 65-140 mg/dL, with target time in range goal of 70%.

Interventions

• Drug Insulin
  Insulin will be used in gestational diabetics to control blood glucose levels

Primary outcome measures

• Neonatal Composite Outcome [Time frame: First 28 days of birth]

Secondary outcome measures (12)

• Neonatal Outcome: Gestational Age of Birth [Time frame: Delivery Time]
• Neonatal Outcome: APGAR Score [Time frame: At 1 minute of life and at 5 min of life]
• Neonatal Outcome: Birthweight [Time frame: Delivery Time]
• Neonatal Outcome: Respiratory distress [Time frame: Within first 24 hours after delivery]
• Neonatal Outcome: Admission to Neonatal intensive Care Unit [Time frame: From delivery to discharge from NICU]
• Maternal Outcomes: Maternal hypoglycemia [Time frame: Initiation of insulin to delivery]
• Maternal Outcomes: Shoulder Dystocia [Time frame: At Delivery]
• Maternal Outcomes: Obstetric anal sphincter injury (OASIS) [Time frame: At Delivery]
• Maternal Outcomes: Operative Delivery [Time frame: At Delivery]
• Maternal Outcomes: Cesarean Delivery [Time frame: At Delivery]
• Maternal Outcomes: Postpartum hemorrhage [Time frame: Within 24 hours of delivery]
• Maternal Outcomes: Hypertensive Disorders of Pregnancy [Time frame: From gestational age of 20 weeks during pregnancy to 6 weeks postpartum]

Eligibility criteria

Inclusion criteria

• Live, non-anomalous fetus
• Literacy in English, Spanish, Mandarin, or Arabic
• Patients are also required to provide consent, demonstrate an understanding of the purpose of the study, and agree to the study protocol.

Exclusion criteria

• <18 years at EDD
• pre-existing diabetes or diagnosis of GDM prior to 24 weeks
• multi-fetal gestation
• known major fetal anomaly
• known allergy to insulin
• chronic maternal corticosteroid use
• diagnosis of GDM based on finger sticks alone
• patients who have contraindication to oral glucose tolerance test
• a primary language other than English, Spanish, Mandarin, or Arabic

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 2 centers

• University of Rochester Medical Center — Rochester
• Thomas Jefferson University — Philadelphia

Publications

• Kunarathnam V, Vadakekut ES, Mahdy H. Gestational Diabetes. 2025 Sep 15. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK545196/ PMID 31424780
• Catalano PM, Hauguel-De Mouzon S. Is it time to revisit the Pedersen hypothesis in the face of the obesity epidemic? Am J Obstet Gynecol. 2011 Jun;204(6):479-87. doi: 10.1016/j.ajog.2010.11.039. Epub 2011 Feb 2. PMID 21288502
• Gregory EC, Ely DM. Trends and Characteristics in Gestational Diabetes: United States, 2016-2020. Natl Vital Stat Rep. 2022 Jul;71(3):1-15. PMID 35877134
• Metzger BE, Persson B, Lowe LP, Dyer AR, Cruickshank JK, Deerochanawong C, Halliday HL, Hennis AJ, Liley H, Ng PC, Coustan DR, Hadden DR, Hod M, Oats JJ, Trimble ER; HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcome study: neonatal glycemia. Pediatrics. 2010 Dec;126(6):e1545-52. doi: 10.1542/peds.2009-2257. Epub 2010 Nov 15. PMID 21078733
• ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018 Feb;131(2):e49-e64. doi: 10.1097/AOG.0000000000002501. PMID 29370047
• Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS; Australian Carbohydrate Intolerance Study in Pregnant Women (ACHOIS) Trial Group. Effect of treatment of gestational diabetes mellitus on pregnancy outcomes. N Engl J Med. 2005 Jun 16;352(24):2477-86. doi: 10.1056/NEJMoa042973. Epub 2005 Jun 12. PMID 15951574
• Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, Wapner RJ, Varner MW, Rouse DJ, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Lain KY, Sorokin Y, Peaceman AM, Tolosa JE, Anderson GB; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. A multicenter, randomized trial of treatment for mild gestational diabete PMID 19797280
• Hartling L, Dryden DM, Guthrie A, Muise M, Vandermeer B, Donovan L. Benefits and harms of treating gestational diabetes mellitus: a systematic review and meta-analysis for the U.S. Preventive Services Task Force and the National Institutes of Health Office of Medical Applications of Research. Ann Intern Med. 2013 Jul 16;159(2):123-9. doi: 10.7326/0003-4819-159-2-201307160-00661. PMID 23712381

Identifiers

NCT: NCT06419803 · iRISID-2024-3181

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗