A meta-analysis of metformin and insulin on maternal outcome and neonatal outcome in patients with gestational diabetes mellitus

Figures & data

Figure 1. Flow chart for the selection of relevant studies.

Table 1. Basic characteristics of the eligible studies.

Study	Year	Country	Gestational weeks	Metformin group	Insulin required	Insulin group
Rowan JA	2008	New Zealand	20–33	363	168	370
Ijäs H	2011	Finland	12–34	47	15	50
Ainuddin J	2012	Pakistan	20–35	75	18	75
Niromanesh S	2012	Iran	20–34	80	11	80
Mesdaghinia E	2013	Iran	24–34	100	22	100
Spaulonci CP	2013	Brazil	NA	46	12	46
Tertti K	2013	Finland	22–34	110	23	107
Ruholamin S	2014	Iran	24–33	50	0	50
Tertti K	2014	Finland	22–34	58	23	107
Ainuddin J	2015	Pakistan	20–36	75	32	75
Ashoush S	2016	Egypt	26–32	48	11	47
Saleh HS	2016	America	26–34	67	0	70
Arshad R	2017	Pakistan	NA	25	0	25
Khan RMA	2017	Pakistan	24–32	385	0	385
Eid SR	2018	Egypt	22–30	113	0	116
Simeonova-Krstevska S	2018	Macedonia	23–35	48	0	101
Galal M	2019	Egypt	28–34	52	4	54
Ghomian N	2019	Ireland	24–28	143	0	143
Huhtala M	2020	Finland	30–36	110	23	107
Mansour A	2021	Egypt	24–28	70	0	70
Mir S	2021	Pakistan	20–28	120	0	120
Picón-César	2021	Spain	14–35	94	4	97
Dasari P	2022	India	NA	80	13	80
Saraswat D	2022	Ecuador	24–28	50	0	50

NA: not applicable.

Figure 2. Pooled analysis of preeclampsia.

Figure 3. Pooled analysis of induction of labor.

Figure 4. Pooled analysis of cesarean delivery.

Table 2. Summary of other outcomes.

Outcomes	Metformin group (n/N)	Control group (n/N)	RR (95% CI)	p
Maternal outcomes
Gestational hypertension	118/1502	141/1511	0.84(0.67, 1.06)	.15
Spontaneous vaginal delivery	750/1398	714/1461	1.13(1.00, 1.28)	.05
Emergency cesarean section	142/703	153/716	0.94(0.77, 1.16)	.58
Shoulder dystocia	10/593	16/600	0.65(0.31, 1.39)	.27
Premature birth	152/1807	188/1877	0.92(0.61, 1.39)	.69
Polyhydramnios	14/180	13/186	1.11(0.54, 2.30)	.77
Birth trauma	30/675	35/685	0.87(0.54, 1.39)	.56
Neonatal outcomes
5-min Apgar score < 7	45/812	40/825	1.13(0.76, 1.68)	.55
SGA	91/1196	105/1267	0.93(0.71, 1.22)	.62
RDS	43/1133	59/1149	0.74(0.50, 1.08)	.11
Jaundice	284/1299	267/1358	1.09(0.95, 1.25)	.24
Birth defects	11/311	14/317	0.80(0.37, 1.74)	.57

SGA: small for gestational age; RDS: respiratory distress syndrome.

Figure 5. Pooled analysis of macrosomia.

Figure 6. Pooled analysis of NICU.

Figure 7. Pooled analysis of neonatal hypoglycemia.

Figure 8. Pooled analysis of LGA.

Table 3. Subgroup analysis.

Outcomes	Subgroup	Number of studies	RR (95% CI)	p
Maternal outcomes
Preeclampsia	Metformin plus insulin vs insulin	6	0.70 (0.49, 1.02)	.06
	Metformin alone vs insulin	6	0.58 (0.42, 0.80)	.001
Induction of labor	Metformin plus insulin vs insulin	8	0.93 (0.83, 1.04)	.23
	Metformin alone vs insulin	4	0.91 (0.69, 1.20)	.53
Cesarean delivery	Metformin plus insulin vs insulin	13	0.90 (0.81, 1.00)	.06
	Metformin alone vs insulin	7	0.99 (0.87, 1.13)	.91
Gestational hypertension	Metformin plus insulin vs insulin	9	0.83 (0.63, 1.09)	.18
	Metformin alone vs insulin	2	0.89 (0.57, 1.37)	.6
Spontaneous vaginal delivery	Metformin plus insulin vs insulin	8	1.18 (0.95, 1.47)	.13
	Metformin alone vs insulin	7	1.04 (0.92, 1.18)	.5
Emergency cesarean section	Metformin plus insulin vs insulin	3	0.95 (0.74, 1.22)	.7
	Metformin alone vs insulin	2	0.95 (0.65, 1.38)	.8
Shoulder dystocia	Metformin plus insulin vs insulin	3	0.69 (0.31, 1.50)	.35
	Metformin alone vs insulin	1	0.34 (0.01, 8.15)	.5
Premature birth	Metformin plus insulin vs insulin	9	1.23 (0.88, 1.72)	.22
	Metformin alone vs insulin	6	0.68 (0.31, 1.48)	.33
Birth trauma	Metformin plus insulin vs insulin	3	0.76 (0.41, 1.40)	.38
	Metformin alone vs insulin	1	1.07 (0.50, 2.28)	.84
Neonatal outcomes
Macrosomia	Metformin plus insulin vs insulin	9	0.76 (0.53, 1.09)	.13
	Metformin alone vs insulin	4	0.65 (0.48, 0.88)	.006
NICU	Metformin plus insulin vs insulin	12	0.78 (0.66, 0.90)	.002
	Metformin alone vs insulin	5	0.83 (0.61, 1.14)	.25
Neonatal hypoglycemia	Metformin plus insulin vs insulin	11	0.68 (0.53, 0.88)	.004
	Metformin alone vs insulin	8	0.59 (0.50, 0.69)	0
LGA	Metformin plus insulin vs insulin	10	0.84 (0.70, 1.00)	.06
	Metformin alone vs insulin	3	0.76 (0.49, 1.19)	.24
5-min Apgar score < 7	Metformin plus insulin vs insulin	3	1.09 (0.63, 1.90)	.74
	Metformin alone vs insulin	3	1.14 (0.63, 2.05)	.65
SGA	Metformin plus insulin vs insulin	8	0.98 (0.72, 1.32)	.89
	Metformin alone vs insulin	4	0.77 (0.39, 1.54)	.47
RDS	Metformin plus insulin vs insulin	7	0.79 (0.51, 1.23)	.3
	Metformin alone vs insulin	4	0.62 (0.27, 1.39)	0.25
Jaundice	Metformin plus insulin vs insulin	9	0.76 (0.55, 1.03)	.08
	Metformin alone vs insulin	4	1.16 (0.98, 1.37)	.07
Birth defects	Metformin plus insulin vs insulin	2	0.92 (0.38, 2.23)	.85
	Metformin alone vs insulin	2	0.52 (0.09, 2.78)	.44

NICU: neonatal intensive care unit admission; SGA: small for gestational age; LGA: large for gestational age; RDS: respiratory distress syndrome.

Table 4. The Egger's tests of the results in this meta-analysis.

Outcomes	Egger’s tests (p value)	Publication bias
Gestational hypertension	.149	(−)
Preeclampsia	.415	(−)
Induced labor	.764	(−)
Spontaneous vaginal delivery	.060	(−)
Cesarean section	.355	(−)
Preterm birth	.444	(−)
Macrosomia	.315	(−)
NICU	.330	(−)
Neonatal hypoglycemia	.701	(−)
SGA	.261	(−)
LGA	.150	(−)
RDS	.720	(−)
Jaundice	.006	(+)

NICU: neonatal intensive care unit admission; SGA: small for gestational age; LGA: large for gestational age; RDS: respiratory distress syndrome.

Figure 9. Risk of bias graph.

Figure 10. Risk of bias summary.

Data availability statement

The data generated for this study are available from the corresponding authors upon reasonable request.