Treatments for women with gestational diabetes mellitus: an overview of Cochrane systematic reviews.

BACKGROUND: Successful treatments for gestational diabetes mellitus (GDM) have the potential to improve health outcomes for women with GDM and their babies. OBJECTIVES: To provide a comprehensive synthesis of evidence from Cochrane systematic reviews of the benefits and harms associated with interventions for treating GDM on women and their babies. METHODS: We searched the Cochrane Database of Systematic Reviews (5 January 2018) for reviews of treatment/management for women with GDM. Reviews of pregnant women with pre-existing diabetes were excluded.Two overview authors independently assessed reviews for inclusion, quality (AMSTAR; ROBIS), quality of evidence (GRADE), and extracted data. MAIN RESULTS: We included 14 reviews. Of these, 10 provided relevant high-quality and low-risk of bias data (AMSTAR and ROBIS) from 128 randomised controlled trials (RCTs), 27 comparisons, 17,984 women, 16,305 babies, and 1441 children. Evidence ranged from high- to very low-quality (GRADE). Only one effective intervention was found for treating women with GDM.EffectiveLifestyle versus usual careLifestyle intervention versus usual care probably reduces large-for-gestational age (risk ratio (RR) 0.60, 95% confidence interval (CI) 0.50 to 0.71; 6 RCTs, N = 2994; GRADE moderate-quality).PromisingNo evidence for any outcome for any comparison could be classified to this category.Ineffective or possibly harmful Lifestyle versus usual careLifestyle intervention versus usual care probably increases the risk of induction of labour (IOL) suggesting possible harm (average RR 1.20, 95% CI 0.99 to 1.46; 4 RCTs, N = 2699; GRADE moderate-quality).Exercise versus controlExercise intervention versus control for return to pre-pregnancy weight suggested ineffectiveness (body mass index, BMI) MD 0.11 kg/m², 95% CI -1.04 to 1.26; 3 RCTs, N = 254; GRADE moderate-quality).Insulin versus oral therapyInsulin intervention versus oral therapy probably increases the risk of IOL suggesting possible harm (RR 1.3, 95% CI 0.96 to 1.75; 3 RCTs, N = 348; GRADE moderate-quality).Probably ineffective or harmful interventionsInsulin versus oral therapyFor insulin compared to oral therapy there is probably an increased risk of the hypertensive disorders of pregnancy (RR 1.89, 95% CI 1.14 to 3.12; 4 RCTs, N = 1214; GRADE moderate-quality).InconclusiveLifestyle versus usual careThe evidence for childhood adiposity kg/m² (RR 0.91, 95% CI 0.75 to 1.11; 3 RCTs, N = 767; GRADE moderate-quality) and hypoglycaemia was inconclusive (average RR 0.99, 95% CI 0.65 to 1.52; 6 RCTs, N = 3000; GRADE moderate-quality).Exercise versus controlThe evidence for caesarean section (RR 0.86, 95% CI 0.63 to 1.16; 5 RCTs, N = 316; GRADE moderate quality) and perinatal death or serious morbidity composite was inconclusive (RR 0.56, 95% CI 0.12 to 2.61; 2 RCTs, N = 169; GRADE moderate-quality).Insulin versus oral therapyThe evidence for the following outcomes was inconclusive: pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 RCTs, N = 2060), caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 RCTs, N = 1988), large-for-gestational age (average RR 1.01, 95% CI 0.76 to 1.35; 13 RCTs, N = 2352), and perinatal death or serious morbidity composite (RR 1.03; 95% CI 0.84 to 1.26; 2 RCTs, N = 760). GRADE assessment was moderate-quality for these outcomes.Insulin versus dietThe evidence for perinatal mortality was inconclusive (RR 0.74, 95% CI 0.41 to 1.33; 4 RCTs, N = 1137; GRADE moderate-quality).Insulin versus insulinThe evidence for insulin aspart versus lispro for risk of caesarean section was inconclusive (RR 1.00, 95% CI 0.91 to 1.09; 3 RCTs, N = 410; GRADE moderate quality).No conclusions possibleNo conclusions were possible for: lifestyle versus usual care (perineal trauma, postnatal depression, neonatal adiposity, number of antenatal visits/admissions); diet versus control (pre-eclampsia, caesarean section); myo-inositol versus placebo (hypoglycaemia); metformin versus glibenclamide (hypertensive disorders of pregnancy, pregnancy-induced hypertension, death or serious morbidity composite, insulin versus oral therapy (development of type 2 diabetes); intensive management versus routine care (IOL, large-for-gestational age); post- versus pre-prandial glucose monitoring (large-for-gestational age). The evidence ranged from moderate-, low- and very low-quality. AUTHORS' CONCLUSIONS: Currently there is insufficient high-quality evidence about the effects on health outcomes of relevance for women with GDM and their babies for many of the comparisons in this overview comparing treatment interventions for women with GDM. Lifestyle changes (including as a minimum healthy eating, physical activity and self-monitoring of blood sugar levels) was the only intervention that showed possible health improvements for women and their babies. Lifestyle interventions may result in fewer babies being large. Conversely, in terms of harms, lifestyle interventions may also increase the number of inductions. Taking insulin was also associated with an increase in hypertensive disorders, when compared to oral therapy. There was very limited information on long-term health and health services costs. Further high-quality research is needed.

Insulin for the treatment of women with gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with short- and long-term complications for the mother and her infant. Women who are unable to maintain their blood glucose concentration within pre-specified treatment targets with diet and lifestyle interventions will require anti-diabetic pharmacological therapies. This review explores the safety and effectiveness of insulin compared with oral anti-diabetic pharmacological therapies, non-pharmacological interventions and insulin regimens. OBJECTIVES: To evaluate the effects of insulin in treating women with gestational diabetes. SEARCH METHODS: We searched Pregnancy and Childbirth's Trials Register (1 May 2017), ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (1 May 2017) and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (including those published in abstract form) comparing:a) insulin with an oral anti-diabetic pharmacological therapy;b) with a non-pharmacological intervention;c) different insulin analogues;d) different insulin regimens for treating women with diagnosed with GDM.We excluded quasi-randomised and trials including women with pre-existing type 1 or type 2 diabetes. Cross-over trials were not eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, risk of bias, and extracted data. Data were checked for accuracy. MAIN RESULTS: We included 53 relevant studies (103 publications), reporting data for 7381 women. Forty-six of these studies reported data for 6435 infants but our analyses were based on fewer number of studies/participants.Overall, the risk of bias was unclear; 40 of the 53 included trials were not blinded. Overall, the quality of the evidence ranged from moderate to very low quality. The primary reasons for downgrading evidence were imprecision, risk of bias and inconsistency. We report the results for our maternal and infant GRADE outcomes for the main comparison. Insulin versus oral anti-diabetic pharmacological therapyFor the mother, insulin was associated with an increased risk for hypertensive disorders of pregnancy (not defined) compared to oral anti-diabetic pharmacological therapy (risk ratio (RR) 1.89, 95% confidence interval (CI) 1.14 to 3.12; four studies, 1214 women; moderate-quality evidence). There was no clear evidence of a difference between those who had been treated with insulin and those who had been treated with an oral anti-diabetic pharmacological therapy for the risk of pre-eclampsia (RR 1.14, 95% CI 0.86 to 1.52; 10 studies, 2060 women; moderate-quality evidence); the risk of birth by caesarean section (RR 1.03, 95% CI 0.93 to 1.14; 17 studies, 1988 women; moderate-quality evidence); or the risk of developing type 2 diabetes (metformin only) (RR 1.39, 95% CI 0.80 to 2.44; two studies, 754 women; moderate-quality evidence). The risk of undergoing induction of labour for those treated with insulin compared with oral anti-diabetic pharmacological therapy may possibly be increased, although the evidence was not clear (average RR 1.30, 95% CI 0.96 to 1.75; three studies, 348 women; I² = 32%; moderate-quality of evidence). There was no clear evidence of difference in postnatal weight retention between women treated with insulin and those treated with oral anti-diabetic pharmacological therapy (metformin) at six to eight weeks postpartum (MD -1.60 kg, 95% CI -6.34 to 3.14; one study, 167 women; low-quality evidence) or one year postpartum (MD -3.70, 95% CI -8.50 to 1.10; one study, 176 women; low-quality evidence). The outcomes of perineal trauma/tearing or postnatal depression were not reported in the included studies.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, 2352 infants; moderate-quality evidence); the risk of perinatal (fetal and neonatal death) mortality (RR 0.85; 95% CI 0.29 to 2.49; 10 studies, 1463 infants; low-quality evidence);, for the risk of death or serious morbidity composite (RR 1.03, 95% CI 0.84 to 1.26; two studies, 760 infants; moderate-quality evidence); the risk of neonatal hypoglycaemia (average RR 1.14, 95% CI 0.85 to 1.52; 24 studies, 3892 infants; low-quality evidence); neonatal adiposity at birth (% fat mass) (mean difference (MD) 1.6%, 95% CI -3.77 to 0.57; one study, 82 infants; moderate-quality evidence); neonatal adiposity at birth (skinfold sum/mm) (MD 0.8 mm, 95% CI -2.33 to 0.73; random-effects; one study, 82 infants; very low-quality evidence); or childhood adiposity (total percentage fat mass) (MD 0.5%; 95% CI -0.49 to 1.49; one study, 318 children; low-quality evidence). Low-quality evidence also found no clear differences between groups for rates of neurosensory disabilities in later childhood: hearing impairment (RR 0.31, 95% CI 0.01 to 7.49; one study, 93 children), visual impairment (RR 0.31, 95% CI 0.03 to 2.90; one study, 93 children), or any mild developmental delay (RR 1.07, 95% CI 0.33 to 3.44; one study, 93 children). Later infant mortality, and childhood diabetes were not reported as outcomes in the included studies.We also looked at comparisons for regular human insulin versus other insulin analogues, insulin versus diet/standard care, insulin versus exercise and comparisons of insulin regimens, however there was insufficient evidence to determine any differences for many of the key health outcomes. Please refer to the main results for more information about these comparisons. AUTHORS' CONCLUSIONS: The main comparison in this review is insulin versus oral anti-diabetic pharmacological therapies. Insulin and oral anti-diabetic pharmacological therapies have similar effects on key health outcomes. The quality of the evidence ranged from very low to moderate, with downgrading decisions due to imprecision, risk of bias and inconsistency.For the other comparisons of this review (insulin compared with non-pharmacological interventions, different insulin analogies or different insulin regimens), there is insufficient volume of high-quality evidence to determine differences for key health outcomes.Long-term maternal and neonatal outcomes were poorly reported for all comparisons.The evidence suggests that there are minimal harms associated with the effects of treatment with either insulin or oral anti-diabetic pharmacological therapies. The choice to use one or the other may be down to physician or maternal preference, availability or severity of GDM. Further research is needed to explore optimal insulin regimens. Further research could aim to report data for standardised GDM outcomes.