OBJECTIVE 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. RESEARCH DESIGN AND METHODS This study used two health care claims databases (United States, 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. RESULTS 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. CONCLUSIONS 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.

中文翻译：

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患有孕前 2 型糖尿病的女性在怀孕期间使用二甲双胍相关的围产期结局


目的 我们模拟了一项修改后的随机试验（妊娠期 2 型糖尿病女性使用二甲双胍 [MiTy]），比较妊娠前接受二甲双胍加胰岛素治疗的 2 型糖尿病女性在妊娠期间继续使用二甲双胍与停用二甲双胍的围产期结局。研究设计和方法 本研究使用了两个医疗保健索赔数据库（美国，2000-2020 年）。年龄在 18-45 岁、患有 2 型糖尿病且在受孕时接受二甲双胍加胰岛素治疗的孕妇符合资格。主要结局是早产、产伤、新生儿呼吸窘迫、新生儿低血糖和新生儿重症监护室入住的综合结果。次要结局包括主要复合结局的组成部分、妊娠高血压、先兆子痫、母亲低血糖、剖腹产、大于胎龄婴儿、小于胎龄婴儿（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，包括人口特征、合并症和糖尿病进展的指标。结果 在 2,983 名符合条件的患者中，72% 在怀孕期间停止使用二甲双胍。受孕时的平均年龄为 32 岁，并且继续妊娠者中几种合并症的患病率较高。继续治疗者的综合结果风险为 46%，停药者为 48%。调整后的风险比为 0.92 (95% CI 0.81, 1.03)。对于大多数次要结果，治疗之间的风险相似，并且数据库之间的风险一致，但 SGA 除外，该风险仅在商业保险人群的继续治疗者中升高。结论 我们的研究结果与 MiTy 随机试验中报告的结果一致。 怀孕期间继续服用二甲双胍与新生儿复合不良结局的风险增加无关。然而，二甲双胍可能带来的 SGA 风险值得进一步考虑。