Comparative effectiveness trial of metformin versus insulin for the treatment of gestational diabetes in the USA: clinical trial protocol for the multicentre DECIDE study
Maged M Costantine,
Chloe A Zera,
William A Grobman,
Mark B Landon,
Erika Werner,
Ann Scheck McAlearney,
Kartik K Venkatesh,
Anna Bartholomew,
Nasim C Sobhani,
Ashley N Battarbee,
Maisa N Feghali,
Camille E Powe,
Patrick Catalano,
Cora MacPherson,
Rebecca G Clifton,
Donna Gregory,
Anne Trinh,
Lauren G Fiechtner,
Donna Rice,
Sharon Cross,
Huban Kutay,
Steven Gabbe,
Kim Boggess,
Vivek Katukuri,
Kacey Eichelberger,
Tania Esakoff,
Lori Harper,
Anjali Kaimal,
Martha Kole-White,
Hector Mendez-Figueroa,
Malgorzata Mlynarczyk,
Anthony Sciscione,
Lydia Shook,
David M Stamilio,
Samantha Wiegand,
Noelia M Zork,
George Saade
Affiliations
Maged M Costantine
The Ohio State University, Columbus, Ohio, USA
Chloe A Zera
Department of Obstetrics and Gynecology, BIDMC, Boston, Massachusetts, USA
William A Grobman
The Ohio State University, Columbus, Ohio, USA
Mark B Landon
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, USA
Erika Werner
Tufts Medical Center, Boston, Massachusetts, USA
Ann Scheck McAlearney
The Ohio State University, Columbus, Ohio, USA
Kartik K Venkatesh
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, USA
Anna Bartholomew
College of Medicine, The Ohio State University, Columbus, Ohio, USA
Nasim C Sobhani
UCSF, San Francisco, California, USA
Ashley N Battarbee
The University of Alabama, Birmingham, Alabama, USA
Maisa N Feghali
University of Pittsburgh, Pittsburgh, Pennsylvania, USA
Camille E Powe
Massachusetts General Hospital, Boston, Massachusetts, USA
Patrick Catalano
Department of Obstetrics and Gynecology, Tufts University, Medford, Oregon, USA
Cora MacPherson
Department of Epidemiology, George Washington University School of Public Health and Health Services, Washington, District of Columbia, USA
Rebecca G Clifton
George Washington University School of Public Health and Health Services, Washington, District of Columbia, USA
Donna Gregory
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, USA
Anne Trinh
The Ohio State University, Columbus, Ohio, USA
Lauren G Fiechtner
Mass General Hospital for Children, Boston, Massachusetts, USA
Donna Rice
DiabetesSisters, Raleigh, North Carolina, USA
Sharon Cross
The Ohio State University, Columbus, Ohio, USA
Huban Kutay
Department of Obstetrics and Gynecology, The Ohio State University, Columbus, Ohio, USA
Steven Gabbe
Ohio State University College of Medicine, Columbus, Ohio, USA
Kim Boggess
The University of North Carolina, Chapel Hill, North Carolina, USA
Vivek Katukuri
University of New Mexico School of Medicine, Albuquerque, New Mexico, USA
Kacey Eichelberger
Prisma Health, Greenville, South Carolina, USA
Tania Esakoff
Cedars-Sinai Medical Center, Los Angeles, California, USA
Lori Harper
The University of Texas, Austin, Texas, USA
Anjali Kaimal
University of South Florida, Tampa, Florida, USA
Martha Kole-White
Brown University, Providence, Rhode Island, USA
Hector Mendez-Figueroa
The University of Texas Health Science Center, Houston, Texas, USA
Malgorzata Mlynarczyk
EVMS, Norfolk, Virginia, USA
Anthony Sciscione
Christiana Care Health Services Inc, Wilmington, Delaware, USA
Lydia Shook
Massachusetts General Hospital, Boston, Massachusetts, USA
David M Stamilio
Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
Samantha Wiegand
Premier Health Miami Valley Hospital, Dayton, Ohio, USA
Noelia M Zork
Columbia University Irving Medical Center, New York, New York, USA
Introduction Gestational diabetes mellitus (GDM) is one of the most common medical complications of pregnancy. Glycaemic control decreases the risk of adverse pregnancy outcomes for the affected pregnant individual and the infant exposed in utero. One in four individuals with GDM will require pharmacotherapy to achieve glycaemic control. Injectable insulin has been the mainstay of pharmacotherapy. Oral metformin is an alternative option increasingly used in clinical practice. Both insulin and metformin reduce the risk of adverse pregnancy outcomes, but comparative effectiveness data from a well-characterised, adequately powered study of a diverse US population remain lacking. 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 remain to be characterised, including barriers to and facilitators of metformin versus insulin use.Methods and analysis In a two-arm open-label, pragmatic comparative effectiveness randomised controlled trial, we 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. We plan to recruit 1572 pregnant individuals with GDM who need pharmacotherapy at 20 US sites using consistent diagnostic and treatment criteria for oral metformin versus injectable insulin and follow them and their children through delivery to 2 years post partum. More information is available at www.decidestudy.org.Ethics and dissemination The Institutional Review Board at The Ohio State University approved this study (IRB: 2024H0193; date: 7 December 2024). We plan to submit manuscripts describing the results of each study aim, including the pregnancy outcomes, the 2-year follow-up outcomes, and mixed-methods assessment of patient experiences for publication in peer-reviewed journals and presentations at international scientific meetings.Trial registration number NCT06445946.
