Comment: The quality of evidence is downgraded by study limitations.
A Cochrane review [Abstract] 1 included 53 studies with a total of 7381 women with gestational diabetes (GDM). Insulin was associated with an increased likelihood of hypertensive disorders of pregnancy (high blood pressure - not defined) although there was no evidence of any difference in pre-eclampsia, caesarean section, developing type 2 diabetes, or postnatal weight compared with oral anti-diabetic medication (table T1). For the infant, there was no evidence of a clear difference between those whose mothers had been treated with insulin and those treated with oral anti-diabetic pharmacological therapies for the risk of being born large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 studies, n=2352). There was no difference in perinatal death, serious morbidity, neonatal hypoglycaemia, adiposity, or neurosensory disabilities in later childhood, however the evidence is insufficient.
| Outcome | Relative effect (95% CI) | Risk with control - Oral anti-diabetic agent | Risk with intervention - Insulin (95% CI) | №of participants (studies) Quality of evidence |
|---|---|---|---|---|
| Hypertensive disorders of pregnancy (pre-eclampsia) | RR 1.14 (0.86 to 1.52) | 77 per 1000 | 88 per 1000 (66 to 117) | 2060 (10) Moderate |
| Hypertensive disorders of pregnancy (not defined) | RR 1.89(1.14 to 3.12) | 36 per 1000 | 69 per 1000(42 to 114) | 1214(4) Moderate |
| Caesarean section | RR 1.03 (0.93 to 1.14) | 394 per 1000 | 405 per 1000 (366 to 449) | 1988 (17) Moderate |
| Postnatal weight retention or return to pre-pregnancy weight: 6 to 8 weeks postpartum | MD 1.60 kg(-6.34 to 3.14) | The mean weight 80.8 kg | MD 1.6 kg lower (6.34 lower to 3.14 higher) | 167(1)Low |
| Maternal weight one year postpartum | MD 3.70 kg(-8.50 to 1.10) | The mean weight 81.8 kg | MD 3.7 kg lower(8.5 lower to 1.1 higher) | 176(1) Low |
| Induction of labour average | RR 1.30, 95%CI 0.96,to 1.75 | 408 per 1000 | 535 per 1000 (424 to 669) | 348 (3) Moderate |
A meta-analysis 5 assessed outcomes of GDM-pregnancies randomised to treatment with metformin versus insulin and included 28 trials with 3 976 participants. Neonates born to metformin-treated mothers had lower birth weights (mean difference -107.7 g, 95% CI -182.3 to -32.7; 17 trials, n=2816, I² = 83%, p = 0.005) than neonates of insulin-treated mothers. The odds of macrosomia (OR 0.59, 95% CI 0.46 to 0.77; 12 trials, n=2237, p < 0.001) and large for gestational age (OR 0.78, 95% CI 0.62 to 0.99; 9 trials, n=1990, p = 0.04) were lower with metformin compared to insulin. In contrast to the neonatal phase, metformin-exposed infants (18-24 months) were significantly heavier than those in the insulin-exposed group (mean difference 440 g, 95% CI 50 to 830; 2 studies, n=411, I² = 4%, p = 0.03). In mid-childhood (5-9 years), BMI was significantly higher (mean difference 0.78, 95% CI 0.23 to 1.33; 3 studies, n=520, I² = 7%, p = 0.005) following metformin versus insulin exposure.
A network meta-analysis 2 included 32 RCTs assessing 6 kinds of treatments (metformin, metformin plus insulin, insulin, glyburide, acarbose, and placebo). Regarding the incidence of macrosomia and large for gestational age (LGA), metformin had lower incidence than glyburide (OR 0.54 and 0.4). In terms of the incidence of admission to the NICU, insulin had higher incidence compared with glyburide (OR 1.84). As for the incidence of neonatal hypoglycemia, metformin had lower incidence than insulin and glyburide (OR 0.63 and 0.39), and insulin was lower than glyburide (OR 0.62). For mean birth weight, metformin plus insulin was lower than insulin (SMD -0.58), glyburide (SMD -0.74), and placebo (SMD -0.66). Besides, metformin was observed to have lower birth weight than glyburide (SMD 0.26). As for weight gain, metformin and metformin plus insulin were lower than insulin (SMD -0.92 to -1.53). Metformin (plus insulin when required) had the lowest incidence of macrosomia, LGA, respiratory distress syndrome, low gestational age at delivery, and low birth weight.
In a trial 3 108 gestational diabetics were randomized to receive either diet alone or diet plus insulin (20 units NPH and 10 units regular). Blood glucose levels were evaluated weekly in a high-risk clinic where medical and nutritional support and counseling were provided. Among 68 women successfully treated for a minimum of 6 weeks, the mean birth weight, macrosomia rate, and ponderal index were reduced significantly in the insulin-treated group. Insulin reduced birth weights significantly in women with a delivery weight of 200 lb or more (4060 +/- 342 versus 3397 +/- 640 g) and in those with a delivery weight less than 200 lb (3324 +/- 448 versus 3047 +/- 394 g). No patient with good glucose control and a maternal delivery weight under 200 lb had a newborn over 4000 g. Patients failing glycemic control were at greatest risk (30%) for fetal overgrowth whether initially receiving insulin or not.
In another trial 4 119 women with GDM were treated with insulin. Women with GDM were older and more obese than the general pregnant population. The mean total daily dose of insulin prepartum, when fasting blood glucose had been normalized, was 53 (SD +/- 25) units (34 +/- 15 units of rapid-acting and 20 +/- 11 units of medium-acting insulin). Mean duration of treatment was 6.4 weeks. The perinatal mortality was 0.8%, compared with 7.4% in previous pregnancies in the same women. The perinatal morbidity was generally mild and included hypoglycaemia (10.9%), hyperbilirubinaemia requiring treatment (2.5%), shoulder dystocia (2.5%). The rate of macrosomia was reduced in the present pregnancies compared with previous ones in the women with GDM.
Date of latest search:2020-03-22
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