Author (year of publication) | Study design | Country | Participant characteristics | Long acting insulin used | Sample size | Key outcomes (comparison group: intermediate acting insulin) |
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Bartal et al. (2021) [28] | RCT | USA | Women with singleton gestation and type 2 diabetes; gestational diabetes mellitus (GDM) diagnosed before 20 weeks gestation; mean age of 32 years and 88% multiparous; pre-pregnancy BMI of > 30 kg/m2 (83%); mean gestational age at randomization (13 wks) | Detemir | 108 (57-Detemir; 51- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.33 (95% CI 0.13, 0.76) Hypertensive disorder: RR 0.81 (95% CI 0.54, 1.16) Mean (SD) gestational weight gain (kg): 7 (1.83) vs. 9 (1.78) Caesarean section: RR 0.99 (95% CI 0.73, 1.34) Postpartum haemorrhage: RR 1.25 (95% CI 0.50, 3.26) Endometritis: RR 0.80 (95% CI 0.22, 2.91) Wound infection or dehiscence: RR 0.83 (95% CI 0.26, 2.64) Postpartum readmission: RR 1.71 (95% CI 0.63, 5.01) Hospitalization for glucose control: RR 0.89 (95% CI 0.42, 1.87) Induction of labour: RR 0.96 (95% CI 0.66, 1.37) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 37.10 (0.23) vs. 37 (0.55) Preterm (< 37 wks): RR 0.93 (95% CI 0.60, 1.39) Large for gestational age (LGA): RR 1.75 (95% CI 0.92, 3.60) Shoulder dystocia: RR 0.98 (95% CI 0.33, 3.00) Admission to NICU: RR 0.91 (95% CI 0.63, 1.21) Respiratory distress: RR 0.69 (95% CI 0.40, 1.13) Need for mechanical ventilation: RR 0.47 (95% CI 0.17, 1.20) Neonatal hypoglycemia: RR 1.02 (95% CI 0.69, 1.54) Need for I/v glucose: RR 1.24 (95% CI 0.78, 2.10) Mean (SD) birth weight (gm): 3158 (660.2) vs. 2707 (812.7) APGAR < 7 (at 5 min): RR 1.13 (95% CI 0.40, 3.33) Small for gestational age (SGA): RR 0.77 (95% CI 0.32, 1.83) Neonatal hyperbilirubinemia: RR 1.20 (95% CI 0.68, 2.22) |
Chico et al. (2016) [29] | Retrospective cohort | Spain | Women with singleton gestation and type 1 diabetes; Median age of 31 years; Mean pre-pregnancy BMI of 23.9 kg/m2 | Glargine | 1210 (356-glargine; 854- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.89 (95% CI 0.64, 1.25) Hypertensive disorder: RR 0.93 (95% CI 0.66, 1.30) Mean (SD) gestational weight gain (kg): 12 (1.63) vs. 12.5 (1.47) Caesarean section: RR 1.10 (95% CI 0.97, 1.26) Hb A1c (%) (mean, SD): 1st trimester: 6.16 (0.34) vs. 6.33 (0.39) 2nd trimester: 5.70 (0.24) vs. 5.79 (0.27) 3rd trimester: 5.70 (0.25) vs. 5.83 (0.27) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 38 (0.25) vs. 38 (0.24) Preterm (< 37 wks): RR 0.97 (95% CI 0.75, 1.24) Large for gestational age (LGA): RR 0.99 (95% CI 0.85, 1.14) Small for gestational age (SGA): RR 1.21 (95% CI 0.53, 2.81) Shoulder dystocia: RR 0.78 (95% CI 0.31, 1.94) Respiratory distress: RR 0.78 (95% CI 0.52, 1.17) Neonatal hypoglycemia: RR 1.14 (95% CI 0.89, 1.46) Mean (SD) birth weight (gm): 3495 (196.2) vs. 3495 (205.7) APGAR < 7 (at 5 min): RR 0.79 (95% CI 0.35, 1.76) Neonatal sepsis: RR 1.40 (95% CI 0.63, 1.53) Stillbirth: RR 0.37 (95% CI 0.08, 1.65) Perinatal mortality: RR 0.61 (95% CI 0.20, 1.80) Spontaneous abortion: RR 1.25 (95% CI 0.84, 1.86) Congenital malformation: RR 0.83 (95% CI 0.45, 1.55) |
Bartal et al. (2020) [30] | Retrospective cohort | USA | Women with singleton gestation and type 2 diabetes; gestational diabetes mellitus (GDM) diagnosed before 20 weeks gestation; majority aged 20–34 yrs (55%); BMI ≥ 30 kg/m2 (> 75%); 80% multiparous | Insulin analogues (glargine and detemir) | 233 (114-basal insulin analogues; 119- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.72 (95% CI 0.35, 1.45) Hypertensive disorder: RR 0.99 (95% CI 0.63, 1.55) Caesarean section: RR 0.93 (95% CI 0.75, 1.15) Endometritis: RR 2.09 (95% CI 0.39, 11.2) Wound infection or dehiscence: RR 0.10 (95% CI 0.02, 0.80) Hospitalization for glucose control: RR 1.26 (95% CI 0.76, 2.08) Induction of labour: RR 0.89 (95% CI 0.57, 1.37) Hospitalization during pregnancy: RR 1.37 (95% CI 0.92, 2.05) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 36.2 (2.1) vs. 36.1 (2.5) Preterm (< 37 wks): RR 0.93 (95% CI 0.68, 1.26) Large for gestational age (LGA): RR 1.56 (95% CI 0.89, 2.73) Shoulder dystocia: RR 1.39 (95% CI 0.32, 6.08) Admission to NICU: RR 1.06 (95% CI 0.77, 1.46) Respiratory distress: RR 0.58 (95% CI 0.22, 1.55) Need for mechanical ventilation: RR 0.68 (95% CI 0.14, 3.24) Neonatal hypoglycemia: RR 1.30 (95% CI 0.88, 1.92) Mean (SD) birth weight (gm): 3186.1 (751.9) vs. 2993.9 (800.6) APGAR < 7 (at 5 min): RR 3.24 (95% CI 0.43, 24.53) Neonatal sepsis: RR 0.42 (95% CI 0.08, 2.11) Perinatal mortality: RR 1.89 (95% CI 0.27, 13.32) Neonatal hyperbilirubinemia: RR 0.59 (95% CI 0.34, 1.05) |
Herrera et al. (2015) [31] | RCT | USA | Women with singleton gestation; type 2 diabetes (16%), remaining with type 1 diabetes (84%); in majority, GDM diagnosed after 24 weeks gestation (68%); median age of 35 years; Median BMI of 28 kg/m2 | Detemir | 87 (42-Detemir; 45- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.74 (95% CI 0.39, 1.40) Mean (SD) gestational weight gain (kg): 12.6 (6.9) vs. 12.9 (5.3) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 38.9 (0.43) vs. 38.8 (0.25) Mean (SD) birth weight (gm): 3230 (167.5) vs. 3235 (237.5) Neonatal hypoglycemia: RR 0.21 (95% CI 0.01, 4.33) Admission to NICU: RR 0.54 (95% CI 0.14, 2.00) APGAR < 7 (at 5 min): RR 3.21 (95% CI 0.13, 76.6) |
Hod et al. (2014) [32] | RCT | Multicentric | Women with singleton gestation and type 1 diabetes; mean age of 30 years; Mean BMI of 25 kg/m2 | Detemir | 310 (152-Detemir; 158- neutral protamine Hagedorn) | Maternal outcomes Hypertensive disorder: RR 1.49 (95% CI 0.71, 3.09) Caesarean section: RR 0.90 (95% CI 0.74, 1.11) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 38.2 (1.9) vs. 37.8 (1.5) Preterm (< 37 wks): RR 0.71 (95% CI 0.40, 1.26) Large for gestational age (LGA): RR 0.74 (95% CI 0.46, 1.21) SGA: RR 3.06 (95% CI 0.32, 29.1) Neonatal hypoglycemia: RR 0.65 (95% CI 0.32, 1.30) Mean (SD) birth weight (gm): 3504 (645) vs. 3571 (601) Spontaneous abortion: RR 1.27 (95% CI 0.52, 3.14) Perinatal mortality: RR 2.04 (95% CI 0.19, 22.3) Congenital malformation: RR 1.02 (95% CI 0.39, 2.65) |
Ji et al. (2020) [33] | RCT | China | Women with singleton gestation and type 1 diabetes; mean age of 31 years; Mean BMI of 25 kg/m2; mean gestational age at enrolment- 28 wks; type of diabetes (?) | Detemir | 240 (120-Detemir; 120- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.50 (95% CI 0.28, 0.90) HbA1c in 3rd trimester (Mean, SD): 5.66 (0.83) vs. 5.80 (0.81) Hypertensive disorder: RR 0.61 (95% CI 0.33, 1.13) Mean (SD) gestational weight gain (kg): 12.21 (3.84) vs. 11.99 (4.11) Caesarean section: RR 1.05 (95% CI 0.87, 1.28) Wound infection or dehiscence: RR 0.83 (95% CI 0.44, 1.57) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 38.64 (2.19) vs. 38.15 (3.05) Preterm (< 37 wks): RR 0.83 (95% CI 0.44, 1.58) Large for gestational age (LGA): RR 1.00 (95% CI 0.43, 2.31) Admission to NICU: RR 0.92 (95% CI 0.63, 1.35) Respiratory distress: RR 1.00 (95% CI 0.21, 4.85) Neonatal hypoglycemia: RR 0.50 (95% CI 0.18, 1.42) Mean (SD) birth weight (gm): 3257.6 (496.6) vs. 3179.7 (671.8) Congenital malformation: RR 1.00 (95% CI 0.21, 4.85) Neonatal hyperbilirubinemia: RR 0.91 (95% CI 0.69, 1.21) |
Mathiesen et al. (2012) [34] | RCT | Multicentric | Women with singleton gestation and type 1 diabetes; mean age of 30 years; Mean BMI of 25 kg/m2; women with type 1 diabetes | Detemir | 310 (152-Detemir; 158- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 1.11 (95% CI 0.89, 1.38) HbA1c in 3rd trimester (Mean, SD): 6.39 (0.71) vs. 6.44 (0.68) Mean (SD) gestational weight gain (kg): 11.5 (2.5) vs. 11.0 (2.84) |
Sleeman et al. (2019) [35] | Retrospective cohort | USA | Women with singleton gestation and type 2 diabetes (65%); mean age of 31 years; Mean HbA1c at enrolment of 8.0% | Insulin analogues (glargine and detemir) | 63 (44-basal insulin analogues; 19- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 1.73 (95% CI 0.21, 14.5) HbA1c in 3rd trimester (Mean, SD): 6.3 (1.2) vs. 6.5 (1.3) Hypertensive disorder: RR 0.37 (95% CI 0.08, 1.62) Caesarean section: RR 0.96 (95% CI 0.65, 1.42) Foetal/neonatal outcomes Preterm (< 37 wks): RR 0.95 (95% CI 0.51, 1.76) Large for gestational age (LGA): RR 0.74 (95% CI 0.21, 2.55) Admission to NICU: RR 0.74 (95% CI 0.44, 1.23) Respiratory distress: RR 0.66 (95% CI 0.27, 1.64) Neonatal hypoglycemia: RR 1.72 (95% CI 0.91, 3.24) Spontaneous abortion: RR 1.84 (95% CI 0.24, 14.4) Neonatal hyperbilirubinemia: RR 0.66 (95% CI 0.27, 1.64) |
Cianni et al. (2008) [36] | Retrospective cohort | Italy | Women with singleton gestation and type 1 diabetes; mean age of 30.5 years; Mean BMI at enrolment of 24 kg/m2 | Glargine | 101 (43-glargine; 58- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.77 (95% CI 0.24, 2.47) HbA1c in 1st trimester (Mean, SD): 6.77 (1.32) vs. 7.6 (1.09) HbA1c in 3rd trimester (Mean, SD): 6.5 (0.79) vs. 6.5 (0.91) Hypertensive disorder: RR 0.67 (95% CI 0.06, 7.2) Caesarean section: RR 0.99 (95% CI 0.81, 1.22) Mean (SD) gestational weight gain (kg): 14.1 (4.1) vs. 13.3 (4.4) Foetal/neonatal outcomes Large for gestational age (LGA): RR 1.07 (95% CI 0.68, 1.68) Admission to NICU: RR 1.14 (95% CI 0.57, 2.30) Neonatal hypoglycemia: RR 0.81 (95% CI 0.32, 2.05) Congenital malformation: RR 0.87 (95% CI 0.15, 4.97) Neonatal hyperbilirubinemia: RR 0.93 (95% CI 0.44, 1.98) |
Egerman et al. (2009) [37] | Retrospective cohort | USA | Women with singleton gestation; type of diabetes not reported; mean age of 29 years; Mean BMI at enrolment of > 30 kg/m2; mean gestational age at enrolment (19 weeks); majority were multigravida | Glargine | 114 (65-glargine; 49- neutral protamine Hagedorn) | Maternal outcomes Hypertensive disorder: RR 2.01 (95% CI 0.85, 4.76) HbA1c in 3rd trimester (Mean, SD): 7.04 (1.4) vs. 7.48 (2.09) Caesarean section: RR 1.08 (95% CI 0.84, 1.40) Mean (SD) gestational weight gain (kg): 13.06 (9.1) vs. 13.69 (10.6) Foetal/neonatal outcomes Admission to NICU: RR 0.98 (95% CI 0.93, 1.05) Neonatal hypoglycemia: RR 1.19 (95% CI 0.64, 2.22) Congenital malformation: RR 1.08 (95% CI 0.44, 2.63) Respiratory distress: RR 0.75 (95% CI 0.23, 2.46) Shoulder dystocia: RR 0.08 (95% CI 0.01, 1.53) Mean (SD) gestational age (wks): 37.3 (2.8) vs. 37.7 (3.3) Mean (SD) birth weight (gm): 3415 (1231) vs. 3351 (1083) Neonatal hyperbilirubinemia: RR 1.68 (95% CI 0.98, 2.88) |
Fang et al. (2009) [38] | Retrospective cohort | USA | Women with singleton gestation; type of diabetes not reported; mean age of 30 years; majority were multigravida | Glargine | 112 (52-glargine; 60- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 3.45 (95% CI 0.14, 82.9) Hypertensive disorder: RR 0.29 (95% CI 0.03, 2.50) Mean (SD) gestational weight gain (kg): 10.8 (8.1) vs. 11.6 (7.7) Caesarean section: RR 0.87 (95% CI 0.63, 1.20) HbA1c (%), third trimester: 6.55 (0.30) vs. 6.70 (0.21) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 38 (1.0) vs. 37.5 (1.2) Preterm (< 37 wks): RR 0.62 (95% CI 0.27, 1.44) Large for gestational age (LGA): RR 0.77 (95% CI 0.38, 1.56) Admission to NICU: RR 0.32 (95% CI 0.09, 1.07) Respiratory distress: RR 3.45 (95% CI 0.14, 82.9) Neonatal hypoglycemia: RR 0.19 (95% CI 0.02, 1.55) Mean (SD) birth weight (gm): 3501.3 (473.1) vs. 3296.4 (525.6) APGAR < 7 (at 5 min): RR 0.38 (95% CI 0.04, 3.59) Neonatal hyperbilirubinemia: RR 0.48 (95% CI 0.18, 1.27) |
Imbergamo et al. (2008) [39] | Case–control | Italy | Women with singleton gestation; type 1 diabetes; mean age of around 27.5 years | Glargine | 30 (15-glargine; 15- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.71 (95% CI 0.29, 1.75) Hypertensive disorder: RR 1.25 (95% CI 0.41, 3.77) Mean (SD) gestational weight gain (kg): 12.4 (3.8) vs. 13.5 (3.9) Caesarean section: RR 1.00 (95% CI 0.60, 1.66) HbA1c (%), first trimester: 6.86 (0.95) vs. 7.79 (1.13) HbA1c (%), second trimester: 6.16 (0.67) vs. 6.62 (0.80) HbA1c (%), third trimester: 6.23 (0.86) vs. 6.47 (0.95) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 36.42 (2.21) vs. 37.04 (1.27) Large for gestational age (LGA): RR 1.75 (95% CI 0.64, 4.74) Respiratory distress: RR 7.00 (95% CI 0.39, 124.8) Neonatal hypoglycemia: RR 4.00 (95% CI 0.50, 31.7) Mean (SD) birth weight (gm): 3278 (756) vs. 3503 (455) APGAR < 7 (at 5 min): RR 9.00 (95% CI 0.53, 153.8) Neonatal hyperbilirubinemia: RR 5.00 (95% CI 0.26, 96.1) |
Negrato et al. (2010) [40] | Prospective cohort | Brazil | Women with singleton gestation; gestational diabetes mellitus (GDM) diagnosed between 24–28 weeks gestation; mean age of 30 years; women with both pregestational (n = 56) and gestational diabetes (n = 82); type of diabetes not specified | Glargine | 138 (55-glargine; 83- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 0.12 (95% CI 0.01, 2.00) Hypertensive disorder: RR 0.28 (95% CI 0.09, 0.93) Mean (SD) gestational weight gain (kg): 11.2 (9.4) vs. 10.6 (6.8) Caesarean section: RR 0.99 (95% CI 0.92, 1.08) HbA1c (%), third trimester: 6.1 (0.8) vs. 6.1 (0.8) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 37.7 (1.43) vs. 36.6 (4.85) Large for gestational age (LGA): RR 1.04 (95% CI 0.68, 1.58) Small for gestational age (SGA): RR 0.30 (95% CI 0.02, 6.13) Respiratory distress: RR 1.26 (95% CI 0.40, 3.92) Neonatal hypoglycemia: RR 0.57 (95% CI 0.16, 2.04) Mean (SD) birth weight (gm): 3450 (640) vs. 3300 (520) APGAR < 7 (at 5 min): RR 0.50 (95% CI 0.02, 12.06) Neonatal hyperbilirubinemia: RR 0.30 (95% CI 0.04, 2.51) Preterm (< 37 wks): RR 0.78 (95% CI 0.46, 1.32) Admission to NICU: RR 0.41 (95% CI 0.12, 1.41) Congenital malformation: RR 0.30 (95% CI 0.07, 1.33) Perinatal mortality: RR 0.30 (95% CI 0.02, 6.13) |
Poyhonen-Alho et al. (2007) [41] | Retrospective chart review | Finland | Pregnant women with singleton pregnancy and type 1 diabetes; women in both groups did not differ in age, parity, age at diagnosis or duration of diabetes, or occurrence of retinopathy or nephropathy before pregnancy | Glargine | 91 (42-glargine; 49- neutral protamine Hagedorn) | Maternal outcomes Symptomatic hypoglycaemia: RR 2.33 (95% CI 0.45, 12.1) Hypertensive disorder: RR 0.58 (95% CI 0.19, 1.80) Caesarean section: RR 1.03 (95% CI 0.69, 1.53) HbA1c (%), first trimester: 7.6 (0.2) vs. 7.2 (0.3) HbA1c (%), second trimester: 6.7 (0.1) vs. 6.8 (0.3) HbA1c (%), third trimester: 6.9 (0.1) vs. 6.9 (0.2) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 36.0 (0.85) vs. 37.0 (0.50) Respiratory distress: RR 2.04 (95% CI 0.64, 6.49) Neonatal hypoglycemia: RR 0.82 (95% CI 0.45, 1.52) Mean (SD) birth weight (gm): 3796 (101) vs. 3789 (68) Neonatal hyperbilirubinemia: RR 0.89 (95% CI 0.49, 1.61) Preterm: RR 2.33 (95% CI 0.22, 24.8) Congenital malformation: RR 3.49 (95% CI 0.15, 83.4) Perinatal mortality: RR 1.17 (95% CI 0.08, 18.1) Shoulder dystocia: RR 0.39 (95% CI 0.04, 3.60) Neonatal sepsis: RR 1.16 (95% CI 0.17, 7.93) |
Price et al. (2007) [42] | Case-control | UK | Women with singleton gestation with type 1 diabetes; mean age of around 32 years; Majority were pre-obese or obese (BMI > 25 kg/m2; majority were multigravida | Glargine | 64 (32-glargine; 32- neutral protamine Hagedorn) | Maternal outcomes HbA1c (%), third trimester: 6.2 (0.85) vs. 6.1 (0.60) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 38.1 (0.47) vs. 38.1 (0.52) Large for gestational age (LGA): RR 0.92 (95% CI 0.50, 1.70) Respiratory distress: RR 7.00 (95% CI 0.38, 130.3) Neonatal hypoglycemia: RR 1.33 (95% CI 0.65, 2.72) Mean (SD) birth weight (gm): 3537 (520) vs. 3594 (429) Congenital malformation: RR 0.67 (95% CI 0.12, 3.73) Admission to NICU: RR 1.40 (95% CI 0.50, 3.95) |
Smith et al. (2009) [43] | Retrospective chart review | USA | Women with singleton gestation; both type 1 and type 2 diabetes; age range of 25–35 years; majority were multigravida | Glargine | 52 (27-glargine; 25- neutral protamine Hagedorn) | Maternal outcomes Hypertensive disorder: RR 0.37 (95% CI 0.08, 1.74) Caesarean section: RR 1.21 (95% CI 0.75, 1.95) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 36.3 (0.96) vs. 37.0 (0.7) Mean (SD) birth weight (gm): 3294 (189) vs. 3274 (137) Admission to NICU: RR 1.08 (95% CI 0.42, 2.78) APGAR < 7 (at 5 min): RR 2.78 (95% CI 0.12, 65.4) |
Imbergamo et al. (2012) [44] | Case-control | Italy | Women with singleton gestation; type 1 diabetes; mean age of around 29 years | Detemir | 16 (8-detemir; 8- neutral protamine Hagedorn) | Maternal outcomes HbA1c (%), first trimester: 7.38 (0.99) vs. 7.60 (1.33) HbA1c (%), second trimester: 6.58 (0.66) vs. 6.43 (0.77) HbA1c (%), third trimester: 6.77 (1.24) vs. 6.32 (1.15) Mean (SD) gestational weight gain (kg): 14 (3.8) vs. 14.46 (4.5) Symptomatic hypoglycaemia: RR 3.00 (95% CI 0.39, 23.1) Hypertensive disorder: RR 0.14 (95% CI 0.01, 2.38) Foetal/neonatal outcomes Mean (SD) gestational age (wks): 36.50 (0.92) vs. 37.35 (1.55) Large for gestational age (LGA): RR 0.50 (95% CI 0.06, 4.47) Mean (SD) birth weight (gm): 3326 (401) vs. 3489 (572) Neonatal hyperbilirubinemia: RR 5.00 (95% CI 0.28, 90.2) |