DECIDE: A Comparative Effectiveness Trial of Metformin Versus Insulin for the Treatment of Gestational Diabetes
DECIDE
1 other identifier
interventional
1,572
1 country
21
Brief Summary
This is a non-inferiority patient-centered and pragmatic comparative-effectiveness pregnancy randomized controlled trial (RCT) with postpartum maternal and child follow-up through 2 years of 1,572 individuals with gestational diabetes mellitus (GDM) randomized to oral metformin versus injectable insulin. This study will determine if metformin is not inferior to insulin in reducing adverse pregnancy outcomes, is comparably safe for exposed individuals and children, and if patient-reported factors, including facilitators of and barriers to use, differ between metformin and insulin. A total of 1,572 pregnant individuals with GDM who need pharmacotherapy will be recruited at 20 U.S. sites using consistent treatment criteria to metformin versus insulin. Participants and their children will be followed through delivery to two years postpartum.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Aug 2024
Longer than P75 for phase_4
21 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2024
CompletedFirst Posted
Study publicly available on registry
June 6, 2024
CompletedStudy Start
First participant enrolled
August 1, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2029
ExpectedStudy Completion
Last participant's last visit for all outcomes
December 1, 2030
January 7, 2026
January 1, 2026
5.3 years
May 21, 2024
January 6, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
A neonatal composite adverse outcome of large-for-gestational-age (LGA) birthweight, hypoglycemia, hyperbilirubinemia, and/or death.
LGA will be defined as a birthweight ≥90th%tile for gestational age based on a US birth certificate reference adjusted for parity and/or fetal sex. Neonatal hypoglycemia will be defined as a blood glucose \<35 mg/dL or treatment \<24 hours after birth with either IV, PO, or gel glucose therapy. Neonatal hyperbilirubinemia will be defined as treated with phototherapy or exchange transfusion in the first postnatal week and either treatment in the first postnatal week or kernicterus. Fetal or neonatal death can be due to any indication between randomization to hospital discharge or 30 days postnatal if still hospitalized (excluding voluntary pregnancy termination).
LGA at birth. Hypoglycemia <24 hours after birth. Hyperbilirubinemia within the first week after birth. Death between randomization to hospital discharge or 30 days postnatal.
Child body mass index (BMI) at 2 years of age
Child BMI measured in kg/m2 as a continuous measure standardized using U.S. CDC reference adjusted for child sex
2 years of age.
Secondary Outcomes (26)
Hypertensive disorder of pregnancy, HDP (maternal)
Randomization to delivery
Gestational weight gain (maternal)
Initiation of prenatal care to delivery
Mode of delivery (maternal)
At birth
Obstetric perineal/anal sphincter injuries (maternal)
At birth
Preterm birth (child)
At birth
- +21 more secondary outcomes
Study Arms (2)
Metformin
EXPERIMENTALMetformin as either immediate- or extended-release formulations can be utilized, and titrated to a maximum daily dose of 2,500 mg. Participants receiving metformin will have insulin added only if they have not achieved euglycemia for at least 30% of glucose values after generally receiving the maximum daily dose of metformin of 2,500 mg, or in select situations in the setting of participant intolerance due to mild gastrointestinal symptoms. Participants will be asked to continue taking metformin after treatment supplementation with insulin.
Insulin
EXPERIMENTALInsulin will be initiated utilizing clinical standards using trimester-specific weight-based dosing criteria, including both basal and prandial insulins for up to a total of 4 daily injections. Consistent with clinical practice, some people may be managed with a single dose of intermediate- or long-acting insulin at night to treat isolated fasting hyperglycemia, while others may require additional treatment of postprandial hyperglycemia with shorter-acting insulin. The sites' insulin formularies include rapid- (Novolog and Humalog), intermediate- (Humulin N, Novolin N, and NPH), and long-acting insulins (Detemir and Lantus).
Interventions
Eligibility Criteria
You may qualify if:
- Singleton gestation. Twin reduction to singleton, either spontaneously or therapeutically, is eligible if it occurred before 14 weeks gestational age.
- Age 18 years or older
- Gestational age at randomization between 20 0/7 - 33 6/7 weeks based on project gestational age.
- GDM diagnosis less than or equal to 33 6/7 weeks based on project gestational age.
- Requires medication for glucose control defined as ≥ 30% elevated glucose values (either fasting or postprandial or both) prior to randomization per determination of the provider or documented in the medical record.
- Patient willingness and ability to attend 2-year follow-up visit.
You may not qualify if:
- Renal disease (serum creatinine \>1.3 mg/dL) due to the potential impact of metformin on renal function.
- Major structural malformation of the fetus.
- Known fetal aneuploidy based on invasive testing or positive for aneuploidy on cell-free fetal DNA screening.
- Contraindication to metformin or insulin, including: history of lactic acidosis, intractable nausea and vomiting, prior documented allergy and/or anaphylaxis.
- For individuals with GDM diagnosed \<20 0/7 weeks, documented A1c ≥\>6.5% within prior 6 months.
- Pregestational diabetes documented in the medical record or prior A1c\>= 6.5%
- Fasting hyperglycemia \>115 mg/dl for ≥ 50% of fasting glucose values in the past week (due to the high risk of metformin failure with fasting hyperglycemia).
- Enrolled in a trial that influences primary study outcomes (composite neonatal outcome at delivery or childhood body mass index at 2 years).
- Prenatal care or delivery planned at a location where access to the complete electronic medical record will not be available to research staff.
- Language barrier (appropriate translation resources unavailable at the site)
- Participation in this trial in a previous pregnancy. Patients who were screened in a previous pregnancy, but not randomized, may be included.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (21)
University of Alabama
Tuscaloosa, Alabama, 35487, United States
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
University of California San Francisco
San Francisco, California, 94143, United States
University of South Florida
Tampa, Florida, 33620, United States
Tufts University
Boston, Massachusetts, 02111, United States
Massachusetts General Hospital
Boston, Massachusetts, 02114, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Washington University in St. Louis
St Louis, Missouri, 63130, United States
University of New Mexico
Albuquerque, New Mexico, 87131, United States
Columbia University Irving Medical Center
New York, New York, 10032, United States
Wake Forest University
Winston-Salem, North Carolina, 27106, United States
The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine
Columbus, Ohio, 43210, United States
Premier Health - Miami Valley Hospital
Dayton, Ohio, 45409, United States
University of Pennsylvania
Philadelphia, Pennsylvania, 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213, United States
Brown University
Providence, Rhode Island, 02912, United States
University of South Carolina Greenville
Greenville, South Carolina, 29605, United States
University of Texas Austin
Austin, Texas, 78705, United States
Austin Maternal Fetal Medicine
Austin, Texas, 78758, United States
University of Texas Health Science Center
Houston, Texas, 77030, United States
Eastern Virginia Medical School - Old Dominion University
Norfolk, Virginia, 23501, United States
Related Publications (4)
Venkatesh KK, Chiang CW, Castillo WC, Battarbee AN, Donneyong M, Harper LM, Costantine M, Saade G, Werner EF, Boggess KA, Landon MB. Changing patterns in medication prescription for gestational diabetes during a time of guideline change in the USA: a cross-sectional study. BJOG. 2022 Feb;129(3):473-483. doi: 10.1111/1471-0528.16960. Epub 2021 Nov 8.
PMID: 34605130BACKGROUNDVenkatesh KK, Wu J, Trinh A, Cross S, Rice D, Powe CE, Brindle S, Andreatta S, Bartholomew A, MacPherson C, Costantine MM, Saade G, McAlearney AS, Grobman WA, Landon MB. Patient Priorities, Decisional Comfort, and Satisfaction with Metformin versus Insulin for the Treatment of Gestational Diabetes Mellitus. Am J Perinatol. 2024 May;41(S 01):e3170-e3182. doi: 10.1055/s-0043-1777334. Epub 2023 Dec 4.
PMID: 38049101BACKGROUNDVenkatesh KK, Lynch CD, Powe CE, Costantine MM, Thung SF, Gabbe SG, Grobman WA, Landon MB. Risk of Adverse Pregnancy Outcomes Among Pregnant Individuals With Gestational Diabetes by Race and Ethnicity in the United States, 2014-2020. JAMA. 2022 Apr 12;327(14):1356-1367. doi: 10.1001/jama.2022.3189.
PMID: 35412565BACKGROUNDVenkatesh KK, MacPherson C, Clifton RG, Powe CE, Bartholomew A, Gregory D, Trinh A, McAlearney AS, Fiechtner LG, Catalano P, Rice D, Cross S, Kutay H, Gabbe S, Grobman WA, Costantine MM, Battarbee AN, Boggess K, Katukuri V, Eichelberger K, Esakoff T, Feghali MN, Harper L, Kaimal A, Kole-White M, Mendez-Figueroa H, Mlynarczyk M, Sciscione A, Shook L, Sobhani NC, Stamilio DM, Werner E, Wiegand S, Zera CA, Zork NM, Saade G, Landon MB. Comparative effectiveness trial of metformin versus insulin for the treatment of gestational diabetes in the USA: clinical trial protocol for the multicentre DECIDE study. BMJ Open. 2024 Sep 24;14(9):e091176. doi: 10.1136/bmjopen-2024-091176.
PMID: 39317491DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kartik Venkatesh, MD, PhD
Ohio State University
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assistant Professor
Study Record Dates
First Submitted
May 21, 2024
First Posted
June 6, 2024
Study Start
August 1, 2024
Primary Completion (Estimated)
December 1, 2029
Study Completion (Estimated)
December 1, 2030
Last Updated
January 7, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
- Time Frame
- Data will be available on website in March 2030.
- Access Criteria
- Users interested in obtaining these data must complete a Restricted Data Use Agreement, specify the reason for the request, and obtain IRB approval or notice of exemption for their research.
PCORI guidelines for data sharing will be followed, including the release of the Analyzable Data Set. This is the final cleaned and locked data set that contains all the data used in conducting the analyses reported in the PCORI Final Research Report and is de-identified in accordance with the HIPAA Privacy Rule.