DECIDE: A Comparative Effectiveness Trial of Metformin Versus Insulin for the Treatment of Gestational Diabetes

NCT ID: NCT06445946

Last Updated: 2026-01-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

1572 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-01

Study Completion Date

2030-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycemic control decreases the risk of adverse pregnancy outcomes for the pregnant individual with GDM and the infant exposed in utero (1). One in four individuals with GDM will require pharmacotherapy to achieve glycemic control. Insulin has been the mainstay of pharmacotherapy. Metformin is an alternative option increasingly used in clinical practice (2). Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterized, adequately powered, and diverse U.S. population remain lacking (3). Because metformin crosses the placenta, long-term safety data, in particular the risk of childhood obesity, from exposed children are also needed. In addition, the patient-reported experiences of individuals with GDM requiring pharmacotherapy remains to be characterized, including barriers for and facilitators of metformin versus insulin use.

In a two-arm open-label, pragmatic comparative effectiveness randomized controlled trial (RCT), the DECIDE Study will examine whether metformin is not inferior to insulin in reducing adverse pregnancy outcomes and is comparably safe for exposed mothers and children, and whether patient-reported factors, including facilitators of and barriers to use, differ between metformin versus insulin use. The DECIDE Study Consortium will recruit and retain 1,572 pregnant individuals with GDM who need pharmacotherapy at 20 U.S. sites to metformin versus insulin and follow them and their children through delivery and then to 2-years

Primary aim:

To evaluate whether outcomes in pregnant individuals randomized to metformin are not inferior to those in pregnant individuals randomized to insulin for the composite adverse neonatal outcome defined as large-for-gestational-age birthweight (LGA), hypoglycemia, hyperbilirubinemia, or death.

Secondary aims:

1. To evaluate whether mean child body mass index (BMI) at 2 years of age is higher in the offspring of pregnant individuals randomized to metformin.
2. To conduct a qualitative or mixed-methods analyses on a subgroup of participants to understand facilitators and barriers associated with metformin versus insulin use and heterogeneity of treatment effects (HTE) to facilitate evidence-based pharmacotherapy.
3. To evaluate whether pregnant individuals randomized to metformin have equivalent maternal (hypertensive disorder of pregnancy, gestational weight gain, mode of delivery, and obstetric anal sphincter injuries) and neonatal (preterm birth, mechanical ventilation, NICU admission, oxygen support, and respiratory distress syndrome) outcomes.
4. To evaluate whether pregnant individuals randomized to metformin have equivalent maternal (obesity, anthropometry, adiposity, diabetes, hypertension, cholesterol, and metabolic profile) and child (obesity, anthropometry, and adiposity) outcomes at 2-years postpartum.
5. To evaluate whether pregnant individuals randomized to metformin have equivalent patient-reported outcomes (PROs), as measured at 6 weeks postpartum and at 2 years postpartum.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Gestational Diabetes Mellitus Pregnancy, High Risk

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Metformin

Metformin 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.

Group Type EXPERIMENTAL

Metformin

Intervention Type DRUG

Individuals randomized to this arm will receive oral metformin tablets for their Gestational diabetes mellitus treatment.

Insulin

Insulin 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).

Group Type EXPERIMENTAL

Insulin

Intervention Type DRUG

Individuals randomized to this arm will receive injectable insulin for their Gestational diabetes mellitus treatment.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Metformin

Individuals randomized to this arm will receive oral metformin tablets for their Gestational diabetes mellitus treatment.

Intervention Type DRUG

Insulin

Individuals randomized to this arm will receive injectable insulin for their Gestational diabetes mellitus treatment.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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.

Exclusion Criteria

* 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.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Patient-Centered Outcomes Research Institute

OTHER

Sponsor Role collaborator

The George Washington University Biostatistics Center

OTHER

Sponsor Role collaborator

Ohio State University

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Kartik K Venkatesh

Assistant Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Kartik Venkatesh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

University of Alabama

Tuscaloosa, Alabama, United States

Site Status RECRUITING

Cedars Sinai Medical Center

Los Angeles, California, United States

Site Status RECRUITING

University of California San Francisco

San Francisco, California, United States

Site Status RECRUITING

University of South Florida

Tampa, Florida, United States

Site Status RECRUITING

Tufts University

Boston, Massachusetts, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University in St. Louis

St Louis, Missouri, United States

Site Status NOT_YET_RECRUITING

University of New Mexico

Albuquerque, New Mexico, United States

Site Status RECRUITING

Columbia University Irving Medical Center

New York, New York, United States

Site Status RECRUITING

Wake Forest University

Winston-Salem, North Carolina, United States

Site Status RECRUITING

The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine

Columbus, Ohio, United States

Site Status RECRUITING

Premier Health - Miami Valley Hospital

Dayton, Ohio, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status NOT_YET_RECRUITING

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Brown University

Providence, Rhode Island, United States

Site Status RECRUITING

University of South Carolina Greenville

Greenville, South Carolina, United States

Site Status RECRUITING

University of Texas Austin

Austin, Texas, United States

Site Status RECRUITING

Austin Maternal Fetal Medicine

Austin, Texas, United States

Site Status NOT_YET_RECRUITING

University of Texas Health Science Center

Houston, Texas, United States

Site Status RECRUITING

Eastern Virginia Medical School - Old Dominion University

Norfolk, Virginia, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Kartik Venkatesh, MD, PhD

Role: CONTACT

614-293-2222

Anna Bartholomew, MPH, BS, RN

Role: CONTACT

614-685-3229

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Ashley Battarbee, MD

Role: primary

Michael Jordan

Role: backup

Tania Esakoff, MD

Role: primary

Marla Sharp

Role: backup

Nasim Sobhani, MD

Role: primary

Magie Fong

Role: backup

Anjali Kaimal Kaimal, MD

Role: primary

Maha Jumaily

Role: backup

Erika Werner, MD

Role: primary

Beth Marsh

Role: backup

Lydia Shook, MD

Role: primary

Nancy Kingori

Role: backup

Chloe Zera, MD

Role: primary

Andy Ngyuen

Role: backup

Megan Lawlor, MD

Role: primary

Emily Diveley, BSN, RN

Role: backup

314-362-4685

Vivek Katukuri, MD

Role: primary

Karen Taylor

Role: backup

Noelia Zork, MD

Role: primary

Joseph Celentano

Role: backup

David Stamilio, MD

Role: primary

Christina Tulbert

Role: backup

Kartik Venkatesh, MD, PhD

Role: primary

614-293-2222

Samantha Wiegand, MD

Role: primary

Emily Reynolds

Role: backup

Celeste Durnwald, MD

Role: primary

215-615-3817

Elizabeth Norton, MPH, MBE

Role: backup

215-615-3817

Maisa Feghali, MD

Role: primary

John Collins

Role: backup

Martha Kole-White, MD

Role: primary

Kelsey Inglesby

Role: backup

Kacey Eichelberger, MD

Role: primary

Patti Parker

Role: backup

Lorie Harper, MD

Role: primary

Mickey Roberts

Role: backup

Mollie McDonnold, MD

Role: primary

512-821-2540

Heather Azarmehr, MSN, RN

Role: backup

737-415-6210

Hector Mendez-Figueroa, MD

Role: primary

Laura Nixon

Role: backup

Malgorzata Mlynarczyk, MD

Role: primary

Cheryl Sparrer

Role: backup

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 34605130 (View on PubMed)

Venkatesh 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.

Reference Type BACKGROUND
PMID: 38049101 (View on PubMed)

Venkatesh 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.

Reference Type BACKGROUND
PMID: 35412565 (View on PubMed)

Venkatesh 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.

Reference Type DERIVED
PMID: 39317491 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2024H0193

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Oral Antidiabetic Agents in Pregnancy
NCT02091336 UNKNOWN PHASE4
Hyperemesis Gravidarum Risk Reduction With Metformin
NCT07129473 NOT_YET_RECRUITING PHASE2