Investigation the Effects of Metformin versus Insulin on Neonatal and Maternal Outcomes in Women with Gestational Diabetes Mellitus: A Randomized Clinical Trail

Abstract

The aim of this study was to evaluate the effectiveness of metformin versus insulin in the glycemic control and to investigate the maternal and neonatal outcomes in in women with gestational diabetes mellitus. Pregnant women with gestational diabetes were randomized to either receive metformin (n=70) or insulin (n=70). Inclusion criteria were singleton pregnancy, following healthy diet and performing exercise for at least one week without satisfactory blood glucose level, no risk factor contributing to lactic acidosis, and no anatomic and/or chromosome anomalies. Two patients were excluded from the study due to lost to follow-up. The mean score of BMI and FBS after treatment was similar between two groups. But, the mean score of 2 hours blood sugar in insulin group (104.38±7.06 mg/dl) was significantly higher than metformin group (97.5±5.98 mg/dl) (P<0.0001). The weight gain in metformin group was slightly lower than insulin group. (P=0.123). The proportion of neonatal hypoglycemia in insulin group was higher than metformin group (20 vs 3, P=0.002). Other neonatal outcomes such as IUGR, IUFD, fetal anomaly, polyhydramnios, macrosomia, oligohydramnios, and NICU stay did not differ significantly between two groups. In conclusion, metformin had compatible effect with insulin in decreasing adverse maternal and neonatal outcomes even in some parameters such as neonatal hypoglycemia it works better. Totally, metformin is safe and effectiveness in controlling the gestational diabetes mellitus.

Metformin for prevention of hypertensive disorders of pregnancy in women with gestational diabetes or obesity: systematic review and meta‐analysis of randomized trials

“…The participants' characteristics varied among the studies, which included women with GDM (13 studies) or obese women (two studies). Metformin was compared with insulin (eight studies), placebo (two studies) or glyburide (five studies) 10,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] . Mean gestational age at randomization and the risk characteristics differed greatly among the studies (Table 1).…”

“…BMI, body mass index; GA, gestational age; GDM, gestational diabetes mellitus; NR, not reported. 31 15 (31.9) 750-2250 NR NR Moore (2010) 27 26 (34.7) 500-2000 NR NR Nachum (2017) 26 9 (17) 850-2250 NR NR Najafian (2017) 38 NR 500-2000 NR 26% of patients were on 2000 mg, 66% were on 1500 mg, 5.9% were on 1000 mg and 1% were on 500 mg Niromanesh (2012) 32 11 (13.8) 1000-2500 NR Median, 1500 mg (IQR: 1000-2500 mg) Pujara (2017) 37 13 (26.0) 500-2500 NR NR Rowan (2008) 33 168 (46.3) 500-2500 69.4% All but one participant received more than 1000 mg, with median dose of 2500 mg Saleh (2016) 39 NR 500-3000 NR NR Silva (2010) 34 8 (25.0) 500-2500 NR Mean ± SD, 1284 ± 535 mg Spaulonci (2013) 35 12 ( First author only is given for each study. *Reported as per individual study protocol.…”

“…We used both random-and fixed-effects models for studies comparing metformin with placebo, which yielded conflicting results. The studies included in this analysis were quite similar in their design and execution, and thus were characterized by low clinical Moore (2010) 27 Nachum (2017) 26 Pujara (2017) 37 Silva (2010) 34 Ainuddin (2014) 28 Ijas (2011) 31 Najafian (2017) 38 Niromanesh (2012) 32 Rowan (2008) 33 Saleh (2016) 39 Spaulonci (2013) 35 Tertti (2013) 36 Chiswick (2015) 29 Syngelaki (2016) Silva (2010) 34 Ainuddin (2014) 28 Niromanesh (2012) 32 Rowan (2008) 33 Tertti (2013) 36 Chiswick (2015) 29 Syngelaki (2016) 10 Summary estimate Moore (2010) 27 Ainuddin (2014) 28 Ijas (2011) 31 Najafian (2017) 38 Niromanesh (2012) 32 Rowan (2008) 33 Saleh (2016) 39 Spaulonci (2013) 35 Tertti (2013) 36 Chiswick (2015) 29 Syngelaki (2016) heterogeneity but high statistical heterogeneity. However, it is unlikely that the summary estimates presented by either method are good representations of the real effect.…”

Metformin for Prevention of Hypertensive Disorders of Pregnancy in Women With Gestational Diabetes or Obesity: Systematic Review and Meta-analysis of Randomized Trials

“…The posterior probability (fixed-effects Bayesian model) of a beneficial effect was 99.4% (odds ratio (OR), 0.54; 95% credible intervals (CrI), 0.25-0.95). 29 -500-2500 65.3% 2500 mg and 2000 mg doses were taken during 38% and 62% of all possible drug taking days, respectively George (2015) 30 0 (0) 500-2500 NR Maximum daily dose was 500 mg in 58.7%, 1000 mg in 21.3% and > 1000 mg in 20.0% of participants Ijas (2011) 31 15 (31.9) 750-2250 NR NR Moore (2010) 27 26 (34.7) 500-2000 NR NR Nachum (2017) 26 9 (17) 850-2250 NR NR Najafian (2017) 38 NR 500-2000 NR 26% of patients were on 2000 mg, 66% were on 1500 mg, 5.9% were on 1000 mg and 1% were on 500 mg Niromanesh (2012) 32 11 (13.8) 1000-2500 NR Median, 1500 mg (IQR: 1000-2500 mg) Pujara (2017) 37 13 (26.0) 500-2500 NR NR Rowan (2008) 33 168 (46.3) 500-2500 69.4% All but one participant received more than 1000 mg, with median dose of 2500 mg Saleh (2016) 39 NR 500-3000 NR NR Silva (2010) 34 8 (25.0) 500-2500 NR Mean ± SD, 1284 ± 535 mg Spaulonci (2013) 35 12 (26.1) 1700-2550 NR Maximum daily dose was 1700 mg in 29.8%, 2550 mg in 42.6% of participants Syngelaki (2016) 10 -1000-3000 79.5% Maximum daily dose was 3000 mg in 63.5%, 2500 mg in 14.2% and 2000 mg in 22.2% of participants Tertti (2013) 36 23 (20.9) 500-2000 NR Median, 1500 mg (IQR: 500-2000 mg)…”

“…The participants' characteristics varied among the studies, which included women with GDM (13 studies) or obese women (two studies). Metformin was compared with insulin (eight studies), placebo (two studies) or glyburide (five studies) 10,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] . Mean gestational age at randomization and the risk characteristics differed greatly among the studies (Table 1).…”