Table 3.
Summary of published meta-analysis comparing metformin with insulin or glyburide in GDM.
| Author, year | Comparison groups, patient number | Maternal outcomes | Fetal outcomes |
|---|---|---|---|
| Gui et al., 2013 [42] | 5 RCTs, 1270 participants; metformin versus insulin | Lower maternal weight gain (p=0.003), lower incidence of PIH (OR 0.52, 95% CI: 0.30–0.90), lower gestational age (p=0.02) at delivery with metformin. | Higher incidence of preterm birth with metformin (OR 1.74, 95% CI: 1.13–2.68). |
| Poolsup, 2014 [43] | 13 RCTs, 2151 patients; oral antidiabetics versus insulin | Significantly lower PPG with metformin. Decreased risk of gestational hypertension with metformin. |
Significant increase in preterm births with metformin. Higher risk of macrosomia and neonatal hypoglycemia with glyburide. |
| Su et al., 2014 [44] | 6 RCTs, 1420 subjects; metformin versus insulin | No increase in adverse maternal outcomes. Less maternal weight gain with metformin. |
Less incidence of neonatal hypoglycemia and higher incidence of premature birth with metformin. |
| Jiang et al., 2015 [45] | 18 RCTs, network meta-analysis. Metformin, insulin, glyburide and acarbose |
No difference in glycemic control. Compared to insulin, metformin was associated with lower maternal weight gain, shorter gestational age and greater premature birth. Compared to glyburide, metformin was associated with less maternal weight gain. |
Metformin was associated with shorter gestational age compared to insulin. Metformin was associated with lower neonatal birth weight, less risk of macrosomia and less risk of neonatal hypoglycemia than glyburide. |
| Kitwitee et al., 2015 [46] | 8 RCTs, 1712 women with GDM; metformin versus Insulin | Similar glycemic control and maternal outcomes. 14–46% required additional insulin. Pooled risk for PIH lower with metformin (RR 0.62, 95% CI: 0.38–1.02, p=0.06). Lower maternal weight gain with metformin (SMD −0.52, 95% CI: −0.78 to −0.26, p<0.01). Lower average gestational age at delivery with metformin (SMD −0.13, 95% CI: −0.23 to −0.03, p<0.01). Nonsignificant increase in preterm deliveries (RR 1.34, 95% CI: 0.73–2.46) with metformin. |
Lower incidence of neonatal hypoglycemia (RR 0.74, 95% CI: 0.58–0.93, p=0.01) and NICU admissions (RR 0.76, 95% CI: 0.59–0.97, p=0.03) with metformin. 98% probability that metformin was superior to insulin for these two neonatal complications. Incidence of LGA babies lower with metformin (RR 0.79; 95% CI: 0.63–1.01, p=0.06). |
| Li et al., 2015 [47] | 11 RCTs; metformin versus insulin | No difference in glycemic control or incidence of preeclampsia. Less risk of PIH (RR 0.53, 95% CI: 0.31–0.90, p=0.02) with metformin. Less maternal weight gain (MD −1.28, 95% CI: −1.54 to −1.01, p<0.0001) with metformin. Lower gestational age at delivery (MD 0.94, 95% CI: −0.21 to −0.01, p=0.03) with metformin. |
Lower birth weight (MD −44.35, 95% CI: −85.79 to −2.90, p=0.04) with metformin. Lower incidence of hypoglycemia (RR 0.69, 95% CI: 0.55–0.87, p<0.001) with metformin. Lower rates of NICU admission (RR 0.82, 95% CI: 0.67–0.99) with metformin. |
| Amin et al., 2015 [48] | 3 RCTs, 508 patients; glyburide versus metformin | No difference in rates of Caesarian section. Significant decrease in fasting glucose with glyburide (MD −2.4 mg/dL, 95% CI: −4.60 to −0.21, p=0.03). |
Increased risk of macrosomia and LGA with glyburide (RR 1.94, 95% CI: 1.03–3.66, p=0.04). Nonsignificant increase in risk of neonatal hypoglycemia (RR 1.92, 95% CI: 0.31–12.02) with glyburide. No difference in preterm births or neonatal birth weight. |
| Balsells et al., 2015 [49] | 15 RCTs, 2509 subjects; two compared metformin with glyburide (349 subjects). six compared metformin with insulin (1362 subjects). |
Metformin versus insulin: less maternal weight gain (−1.14 kg, 95% CI: −2.22 to −0.06). Lower postprandial glucose (MD −0.14 mmol/l, 95% CI: −0.22 to −0.05). Lower incidence of PIH (RR 0.53, 95% CI: 0.31–0.90). Less gestational age at delivery (MD −0.16 weeks, 95% CI: −0.30 to −0.02). Treatment failure with metformin 33.8%. Metformin versus glyburide: less maternal weight gain (MD −2.06 kg, 95% CI: −3.98 to −0.14). Treatment failure higher with metformin (26.8 versus 23.5%). |
Metformin versus insulin: less risk of neonatal hypoglycemia (RR 0.78, 95% CI: 0.60–1.01). Higher preterm births (RR 1.50, 95% CI: 1.04–2.16). Metformin versus glyburide: lower birth weight (MD −209 g, 95% CI: −314 to −104), less risk of macrosomia (RR 0.33, 95% CI: 0.13–0.81) and LGA (RR 0.44, 95% CI: 0.21–0.92). |
| Singh et al., 2015 [50] | 7 RCTs, 1514 women; metformin versus insulin | No difference in glycemic control. Less maternal weight gain with metformin in four studies. Higher preterm births with metformin in one study. No difference in other maternal outcomes. |
No difference in neonatal outcomes. |
| Zhu et al., 2016 [51] | 8 RCTs, 1712 GDM women; metformin (n=853) versus insulin (n=859) | No difference in glycemic control; 15–46% required insulin. No increased risk of prematurity. Metformin – reduced risk of PIH and less maternal weight gain. |
Reduced risk of neonatal hypoglycemia and NICU admissions. No difference in other neonatal outcomes. |
| Liang et al., 2017 [52] | 32 RCTs, network meta-analysis. Metformin, insulin, glyburide, metformin plus glyburide, acarbose and placebo |
Metformin had lower maternal weight gain than insulin. Ranking results – metformin had lowest incidence of PIH but lower gestational age at delivery. |
Metformin had lower incidence of neonatal hypoglycemia compared to insulin or glyburide. Metformin had lower birth weight and lower incidence of macrosomia and LGA compared to glyburide. Ranking – metformin had lower birth weight and lowest incidence of macrosomia, LGA, RDS. |
| Brown et al., 2017 [53] | 11 RCTs comparing oral antidiabetics with placebo or other oral antidiabetics. Trials including insulin were excluded. | Metformin versus glyburide: no difference in maternal outcomes. | Metformin versus glyburide: decrease in death or serious morbidity composite. No difference in risk of LGA or neonatal hypoglycemia or perinatal mortality. Overall data insufficient to recommend one oral antidiabetic over another. |
| Brown et al., 2017 [54] | 53 studies, 7381 participants. Insulin compared to oral antidiabetics. |
Insulin associated with increased risk of hypertensive disorders of pregnancy compared to OADs. No difference in rates of preeclampsia or Caesarian section. | No difference in risk of LGA, perinatal mortality or serious morbidity, neonatal hypoglycemia or neonatal adiposity. Low quality evidence of no difference in neurosensory outcomes in offspring. |
| Feng et al., 2017 [55] | RCTs comparing insulin and metformin. | No difference in gestational age and Caesarian section. Lower maternal weight gain and HbA1c at 36–37 weeks with metformin. Lower rates of gestational hypertension with metformin. | No difference in neonatal respiratory distress and preterm birth or other neonatal outcomes. |
| Farrar et al., 2017 [56] | Metformin versus insulin – 11 trials. Metformin versus glyburide – 3 trials. Analysis not possible due to paucity of data. |
Lower risk of preeclampsia, PIH, induction of labor and instrumental delivery with metformin compared to insulin. | Lower risk of LGA, macrosomia, NICU admissions, neonatal hypoglycemia with metformin compared to insulin. Lower risk of LGA with metformin compared to glyburide. |
| Butalia et al., 2017 [57] | 16 studies, 2165 participants; metformin versus insulin. | Lower risk of PIH with metformin, RR 0.56; 95% CI: 0.37–0.85. Lower maternal weight gain with metformin, MD −2.07; 95% CI: −2.88 to −1.27. Metformin did not increase preterm delivery, RR 1.18; 95% CI: 0.67–2.07. No difference in rates of Caesarian section. |
Lower risk of neonatal hypoglycemia with metformin, RR 0.63; 95% CI: 0.45–0.87. Lower risk of LGA with metformin, RR 0.80; 95% CI: 0.64–0.99. No difference in perinatal mortality or SGA. |
GDM, gestational diabetes; LGA, large for gestational age; NICU, neonatal intensive care unit; OAD, oral antidiabetic drugs; OR, odds ratio; PIH, pregnancy-induced hypertension; PPG, postprandial plasma glucose; RCTs, randomized controlled trials; RDS, respiratory distress syndrome; RR, relative risk; SGA, small for gestational age; SMD, standardized mean difference.