Comparison of Insulin, Metformin, and Glyburide on Perinatal Complications of Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis

Abstract

<b><i>Aim:</i></b> This systematic and meta-analysis was conducted to evaluate the efficacy and safety of insulin, metformin, and glyburide on perinatal complications for gestational diabetes mellitus (GDM). <b><i>Methods:</i></b> Medline (PubMed), EMBASE, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials [CENTRAL], and Cochrane Methodology Register), Web of Science (Science and Social Science Citation Index), and ClinicalTrials (Clinicaltrials.gov) were searched, as well as manual searching. We included randomized controlled trials comparing efficacy and safety of metformin versus glyburide, metformin versus insulin, and glyburide versus insulin in patients with GDM. <b><i>Results:</i></b> We included 32 articles including 5,964 patients published from inception to July 2020. Compared with insulin, metformin was more effective at lower incidence of macrosomia (RR: 0.66, 95% CI: 0.50–0.88, <i>p</i> = 0.005), lower incidence of neonatal intensive care unit admission (RR: 0.78, 95% CI: 0.67–0.91, <i>p</i> = 0.002), less neonatal hypoglycemia (RR: 0.67, 95% CI: 0.56–0.80, <i>p</i> < 0.0001), decreased birth weight (BW) (SMD: −0.37, 95% CI: −0.62 to −0.12, <i>p</i> = 0.004), lower incidence of large for gestational age (RR: 0.76, 95% CI: 0.50–0.90, <i>p</i> = 0.002), shorter gestation age at delivery (MD: −0.22, 95% CI: −0.34 to −0.10, <i>p</i> = 0.0002), lower maternal weight gain (MD: −1.41, 95% CI: −2.28 to −0.55, <i>p</i> = 0.001), less incidence of caesarean section delivery (RR: 0.86, 95% CI: 0.78–0.95, <i>p</i> = 0.0004), lower maternal postprandial blood glucose (SMD: −0.41, 95% CI: −0.72 to −0.11, <i>p</i> = 0.008), and lower incidence of pregnancy-induced hypertension (RR: 0.47, 95% CI: 0.27–0.83, <i>p</i> = 0.01). However, glyburide, compared with insulin, was associated with higher BW (MD: 54.95, 95% CI: 3.87–106.03, <i>p</i> = 0.03) and increased the incidence of neonatal hypoglycemia (RR: 1.52, 95% CI: 1.12–2.07, <i>p</i> = 0.007). Meanwhile, compared to glyburide, metformin was associated with higher maternal fasting blood glucose (SMD: 0.20, 95% CI: 0.05–0.36, <i>p</i> = 0.01) and lower incidence of induction of labor (RR: 0.76, 95% CI: 0.59–0.97, <i>p</i> = 0.03). <b><i>Conclusions:</i></b> This review suggests that metformin can decrease the incidence of perinatal complications, and it should be considered as a generally safe alternative to insulin.

Effects of Different Glucose-Lowering Measures on Maternal and Infant Outcomes in Pregnant Women with Gestational Diabetes: A Network Meta-analysis

“…However, opinions regarding the effect of metformin for GDM on maternal and infant outcomes vary. In our study, both DMA and NMA demonstrated that metformin reduced the incidences of neonatal hypoglycemia and NICU admission compared to insulin, and SUCRA sequencing found that the incidence of neonatal hypoglycemia was lowest in the metformin group, consistent with a previous meta-analysis by Wang et al [68][69][70][71][72]. Since glucose can pass through the placenta, high maternal blood glucose leads to increased fetal glucose levels, resulting in excessive insulin secretion in the fetus.…”

“…However, Tarry et al [80] suggested that metformin increases the risk of macrosomia in offspring, whereas the study by Wang et al produced conflicting results. Their results suggest that metformin can reduce the incidences of macrosomia, cesarean section, and gestational hypertension compared with insulin treatment in pregnant women with GDM [68,69]. The main reason behind the differences between the results of the analyses may be that the inclusion and exclusion criteria applied were inconsistent across studies, leading to certain differences between the data in the included literature and, in turn, to differing research results.…”

Immunoendocrine Dysregulation during Gestational Diabetes Mellitus: The Central Role of the Placenta

“…Recent studies showed a lower risk for preeclampsia, macrosomia, neonatal hypoglycemia, and hypertensive disorders as well as better outcomes in maternal weight gain and glycemic control. No difference was observed in rates of caesarean section, neonatal respiratory distress and preterm birth compared to insulin treatment alone [ 13 , 14 , 15 , 16 , 17 ]. There is insufficient evidence on the long-term effects of prenatal exposure to metformin (especially because it crosses the placenta).…”

Influence of Maternal Diabetes on the Risk of Neurodevelopmental Disorders in Offspring in the Prenatal and Postnatal Periods

“…Unlike the aforementioned study, insulin was the only antidiabetic medication used in our cohort. In contrast to insulin [ 22 ], other antidiabetic medications such as metformin or glyburide are known to cross the placenta and have been associated with adverse neonatal outcomes such as preterm birth and neonatal hypoglycemia, respectively [ 23 - 25 ]. Thus, the effect of antidiabetic medication on neurodevelopment, indirectly as a consequence of adverse neonatal outcomes or through direct interference with fetal brain development, could not be ruled out in the previous studies.…”