DECIDE: A Comparative Effectiveness Trial of Oral Metformin Versus Injectable Insulin for the Treatment of Gestational Diabetes
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 1,572
- 试验地点
- 31
- 主要终点
- A neonatal composite adverse outcome of large-for-gestational-age (LGA) birthweight, hypoglycemia, hyperbilirubinemia, and/or death.
研究概览
简要总结
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.
详细描述
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:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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).
干预措施: Insulin (Drug)
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.
干预措施: Metformin (Drug)
结局指标
主要结局
A neonatal composite adverse outcome of large-for-gestational-age (LGA) birthweight, hypoglycemia, hyperbilirubinemia, and/or death.
时间窗: 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.
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).
Child body mass index (BMI) at 2 years of age
时间窗: 2 years of age.
Child BMI measured in kg/m2 as a continuous measure standardized using U.S. CDC reference adjusted for child sex
次要结局
- Prediabetes (maternal)(2-year follow-up.)
- Hypertension (maternal)(2-year follow-up.)
- Cholesterol (maternal)(2-year follow-up.)
- Hemoglobin A1c (maternal)(2-year follow-up.)
- Overweight (child)(2-year follow-up.)
- Obesity (child)(2-year follow-up.)
- Anthropometry (child)(2-year follow-up.)
- Obstetric perineal/anal sphincter injuries (maternal)(At birth)
- Preterm birth (child)(At birth)
- Requiring mechanical ventilation (child)(<72 hours after birth)
- Mode of delivery (maternal)(At birth)
- Oxygen support (child)(<72 hours after birth)
- Body mass index (BMI) (maternal)(2-year follow-up)
- Hypertensive disorder of pregnancy, HDP (maternal)(Randomization to delivery)
- Gestational weight gain (maternal)(Initiation of prenatal care to delivery)
- Respiratory distress syndrome (child)(Anytime during the first 72 hours after birth)
- Obesity overall and by class (maternal)(2-year follow-up)
- Type 2 diabetes (maternal)(2-year follow-up.)
- Adiposity (child)(2-year follow-up.)
- Treatment Satisfaction Questionnaire for Medication (TSQM)(6-weeks postpartum.)
- NICU admission (child)(Birth to delivery discharge.)
- Adiposity (maternal)(2 year follow-up)
- Questionnaire on Acceptability of Treatment(6-weeks postpartum.)
- Anthropometry (maternal)(2-year follow-up)
研究者
Kartik K Venkatesh
Assistant Professor
Ohio State University