Department of Epidemiology, Boston University School of Public Health, Boston, MA.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.
Diabetes Care. 2024 Sep 1;47(9):1688-1695. doi: 10.2337/dc23-2056.
We emulated a modified randomized trial (Metformin in Women With Type 2 Diabetes in Pregnancy [MiTy]) to compare the perinatal outcomes in women continuing versus discontinuing metformin during pregnancy among those with type 2 diabetes treated with metformin plus insulin before pregnancy.
This study used two health care claims databases (U.S., 2000-2020). Pregnant women age 18-45 years with type 2 diabetes who were treated with metformin plus insulin at conception were eligible. The primary outcome was a composite of preterm birth, birth injury, neonatal respiratory distress, neonatal hypoglycemia, and neonatal intensive care unit admission. Secondary outcomes included the components of the primary composite outcome, gestational hypertension, preeclampsia, maternal hypoglycemia, cesarean delivery, infants large for gestational age, infants small for gestational age (SGA), sepsis, and hyperbilirubinemia. We adjusted for potential baseline confounders, including demographic characteristics, comorbidities, and proxies for diabetes progression.
Of 2,983 eligible patients, 72% discontinued use of metformin during pregnancy. The average age at conception was 32 years, and the prevalence of several comorbidities was higher among continuers. The risk of the composite outcome was 46% for continuers and 48% for discontinuers. The adjusted risk ratio was 0.92 (95% CI 0.81, 1.03). Risks were similar between treatments and consistent between databases for most secondary outcomes, except for SGA, which was elevated in continuers only in the commercially insured population.
Our findings were consistent with those reported in the MiTy randomized trial. Continuing metformin during pregnancy was not associated with increased risk of a neonatal composite adverse outcome. However, a possible metformin-associated risk of SGA warrants further consideration.
我们模拟了一项改良的随机试验（Metformin in Women With Type 2 Diabetes in Pregnancy [MiTy]），以比较在妊娠期间继续或停止使用二甲双胍的 2 型糖尿病女性的围产期结局，这些女性在妊娠前已接受二甲双胍联合胰岛素治疗。
本研究使用了两个医疗保健索赔数据库（美国，2000-2020 年）。符合条件的研究对象为年龄在 18-45 岁之间、患有 2 型糖尿病、在受孕时接受二甲双胍联合胰岛素治疗的孕妇。主要结局是早产、出生损伤、新生儿呼吸窘迫、新生儿低血糖和新生儿重症监护病房入院的复合结局。次要结局包括主要复合结局的组成部分、妊娠期高血压、子痫前期、母体低血糖、剖宫产、胎儿大于胎龄、胎儿小于胎龄（SGA）、败血症和高胆红素血症。我们调整了潜在的基线混杂因素，包括人口统计学特征、合并症和糖尿病进展的替代指标。
在 2983 名符合条件的患者中，有 72%的患者在妊娠期间停止使用二甲双胍。受孕时的平均年龄为 32 岁，继续使用者的几种合并症患病率较高。继续使用者的复合结局风险为 46%，而停止使用者的风险为 48%。调整后的风险比为 0.92（95%CI 0.81, 1.03）。大多数次要结局的治疗风险相似，且在两个数据库之间一致，除了 SGA 外，仅在商业保险人群中继续使用者的 SGA 风险升高。
我们的研究结果与 MiTy 随机试验报告的结果一致。在妊娠期间继续使用二甲双胍与新生儿复合不良结局的风险增加无关。然而，二甲双胍相关的 SGA 风险值得进一步考虑。
