Table 3.
Clinical outcomes in women with gestational diabetes mellitus
| First author_Year | Treatment arms | Sample size | Time points | FBG (mean ± SD) mg/dl or mmol/l | PPG (mean ± SD) mg/dl or mmol/l | 1-h PPG (mean ± SD) mg/dl or mmol/l | 2-h PPG (mean ± SD) mg/dl or mmol/l | 
|---|---|---|---|---|---|---|---|
| RCT | |||||||
| Wasim_2019 [21] | Insulin-Humulin R and NPH | 141 | Baseline | 120 ± 22.4 | NR | NR | NR | 
| Delivery | 96.6 ± 6.2 | NR | NR | NR | |||
| Metformin | 137 | Baseline | 117 ± 18.1; p = 0.215 vs. insulin | NR | NR | NR | |
| Delivery | 92.1 ± 6.0; p = 0.001 vs. insulin | NR | NR | NR | |||
| Galal_2019 [20] | Human insulin | 50 | NA | 92.42 ± 4.93 | 129.82 ± 7.88 | NR | NR | 
| Metformin | 56 | NA;1 week | 86.88 ± 5.02; p = 0.0001 | 117.30 ± 8.84; p = 0.0001 | NR | NR | |
| Eid_2018 [34] | Insulin (NPH + regular insulin) | 116 | Before treatment | 116.83 ± 24.5 | NR | NR | 171.1 ± 41.8 | 
| After treatment | 84.1 ± 3.1 | NR | NR | 101.4 ± 4.8 | |||
| Metformin | 113 | Before treatment | 114.38 ± 19.87; p = 0.64 insulin vs. metformin | NR | NR | 168.9 ± 39.1; p = 0.79 insulin vs. metformin | |
| After treatment | 81.7 ± 3.6, p = 0.065 insulin vs. metformin | NR | NR | 95.9 ± 4.7, p = 0.53 insulin vs. metformin | |||
| Huhtala_2018 [43] | NPH insulin and/or rapid-acting insulin lispro or insulin aspart | 107 | At enrolment | 5.57 ± 0.42 | NR | 11.2 ± 1.24 | 7.91 ± 1.75 | 
| Metformin | 110 | At enrolment | 5.52 ± 0.55; p = 0.44 vs. insulin | NR | 11.2 ± 1.49; p = 0.61 vs. insulin | 8.33 ± 1.76; p = 0.076 vs. insulin | |
| Diet | 103 | At enrolment | 5.38 ± 0.43 | NR | 10.9 ± 1.06 | 7.81 ± 1.91 | |
| Ghomian_2018 [33] | Levemir (insulin detemir) + aspart | 143 | At treatment onset | 92.21 ± 4.41 | NR | NR | 152.58 ± 4.87 | 
| Delivery | 88.03 ± 5.00 | NR | NR | 118.99 ± 6.24 | |||
| Metformin | 143 | At treatment onset | 91.22 ± 4.37; p = 0.57 vs. insulin | NR | NR | 152.25 ± 5.11; p = 0.69 vs. insulin | |
| Delivery | 89.16 ± 3.44; p = 0.79 vs. insulin | NR | NR | 119.38 ± 4.03; p = 0.33 vs. insulin | |||
| Khan_2017 [24] | Insulin (mixed human suspension) | 385 | Before treatment | 122.37 ± 9.94 | NR | NR | 174.46 ± 6.02 | 
| After treatment | 76.88 ± 7.75 | NR | NR | 112.34 ± 5.02 | |||
| Metformin | 385 | Before treatment | 130.06 ± 10.34; t = 10.53; p = 0.000 vs. insulin | NR | NR | 175.18 ± 7.89; t = 1.42; p = 0.157 vs. insulin | |
| After treatment | 82.28 ± 5.51; t = 11.15; p = 0.000 vs. insulin | NR | NR | 111.94 ± 7.02; t = − 0.909; p = 0.364 vs. insulin | |||
| Zawiejska_2016 [23] | Basal-bolus insulin (human recombined insulin) | 43 | At booking | 5.5 ± 0.7 | NR | NR | NR | 
| At term | 4.7 ± 1; p < 0.0001 change from baseline | NR | NR | NR | |||
| Metformin and metformin + insulin | 35 | At booking | 5.8 ± 0.6 | NR | NR | NR | |
| At term | 5.2 ± 0.5; p = 0.004 change from baseline; p (booking) = 0.101; p (at term) = 0.008 vs. insulin | NR | NR | NR | |||
| Behrashi_2016 [67] | Regular insulin and NPH | 129 | NA | 83.75 ± 6.77 | NR | NR | 107.14 ± 7.99 | 
| Glibenclamide | 120 | NA | 84.85 ± 5.26; p = 0.38 vs. insulin | NR | NR | 114.38 ± 81.74; p = 0.95 vs. insulin | |
| Ashoush_2016 [22] | Insulin-control (regular + NPH) | 48 | Baseline | 106.4 ± 4.4 | NR | 208.3 ± 13.2 | 177.6 ± 8.8 | 
| 1 week | 93.5 ± 2.6 | NR | NR | 122.9 ± 7.2 | |||
| First 2 weeks | 103.5 ± 3.5 | NR | NR | 170.5 ± 8.2 | |||
| Last week | 79.9 ± 3.7 | NR | NR | 111.3 ± 4.2 | |||
| Last 2 weeks | 80.8 ± 4.7 | NR | NR | 112.2 ± 6.8 | |||
| Metformin and metformin + insulin-research | 36 + 11 | Baseline | 105.7 ± 4.7, p = 0.417 vs. insulin | NR | 203.9 ± 9.9, p = 0.075 vs. insulin | 175.7 ± 10.0, p = 0.318 vs. insulin | |
| 1 week | 92.8 ± 2.8, p = 0.257 vs. insulin | NR | NR | 120.6 ± 7.8, p = 0.142 vs. insulin | |||
| First 2 weeks | 100.7 ± 3.3; p = 0.014 vs. insulin | NR | NR | 166.9 ± 8.9, p = 0.197 vs. insulin | |||
| Last week | 78 ± 3.1; p = 0.0008 vs. insulin | NR | NR | 109.9 ± 3.7; p = 0.104 vs. insulin | |||
| Last 2 weeks | 78.9 ± 3.5; p = 0.029 vs. insulin | NR | NR | 111 ± 5.2; p = 0.342 vs. insulin | |||
| Somani_2016 [26] | Regular/NPH or both | 33 | Baseline | 102.67 ± 9.61 | NR | 216.61 ± 22.39 | 179.0 ± 20.98 | 
| Delivery | 82.27 ± 5.57 | NR | NR | 113.06 ± 11.71 | |||
| Metformin | 32 | Baseline | 100.03 ± 10.79; p = 0.30 vs. insulin | NR | 215.22 ± 15.34; p = 0.77 vs. insulin | 182.69 ± 17.33; p = 0.44 vs. insulin | |
| Delivery | 85.41 ± 5.96; p = 0.32 vs. insulin | NR | NR | 121.28 ± 11.0; p = 0.005 vs. insulin | |||
| Mirzamoradi_2015 [42] | Insulin (regular + NPH) | 59 | At diagnosis | 112.15 ± 19.39 | NR | NR | NR | 
| At treatment to delivery | 123.42 ± 14.71 | 120.15 ± 9.56 | NR | NR | |||
| Glyburide | 37 | At diagnosis | 109.83 ± 68.99; p = 0.72 vs. glyburide | NR | NR | NR | |
| At treatment to delivery | 114.02 ± 10.65; p = 0.83 vs. glyburide | 115.46 ± 8.21; p = 0.83 vs. glyburide | NR | NR | |||
| Ainuddin_2015 [36] | Insulin (short- + intermediate-acting)-GDM | 75 | Treatment initiation | 172 ± 21.5 | NR | NR | NR | 
| Throughout pregnancy | 97.4 ± 2.5 | NR | NR | NR | |||
| Metformin-GDM | 43 | Treatment initiation | 138 ± 16 | NR | NR | NR | |
| Throughout pregnancy | 96.4 ± 5.7 | NR | NR | NR | |||
| Insulin + metformin-GDM | 32 | Treatment initiation | 144 ± 23 | NR | NR | NR | |
| Throughout pregnancy | 95.3 ± 6.3 | NR | NR | NR | |||
| Arshad_2014 [25] | Regular and NPH | 25 | 1 week of enrolment | 117 ± 29.0 | NR | NR | NR | 
| Diet + exercise | 25 | 1 week of enrolment | 90.96 ± 16.84; p = 0.00 vs. insulin | NR | NR | NR | |
| Mukhopadhyay_2014 [58] | Insulin | 30 | At enrolment | 109.3 ± 19.63 | 194.3 ± 18.47 | NR | NR | 
| Before confinement | 88.17 ± 8.44 | 128 ± 12.38 | NR | NR | |||
| Glibenclamide | 30 | At enrolment | 103 ± 14.62; p = 0.199 vs. insulin | 184.1 ± 20.46; p = 0.048 vs. insulin | NR | NR | |
| Before confinement | 88.23 ± 6.55; p = 0.97 vs. insulin | 122.7 ± 10.3; p = 0.07 vs. insulin | NR | NR | |||
| Mesdaghinia_2012 [56] | NPH and regular | 100 | Baseline | NR | NR | NR | NR | 
| Delivery | NR | NR | NR | NR | |||
| Metformin | 100 | Baseline | NR | NR | NR | NR | |
| Spaulonci_2013 [68] | NPH insulin | 46 | Before treatment | 100.87 ± 15.05 | Breakfast: 119.81 ± 21.59; lunch: 123.72 ± 19.4; dinner: 132.63 ± 23.82 | NR | NR | 
| After treatment | 88.35 ± 7.45 | Breakfast: 106.45 ± 11.75; lunch: 111.43 ± 8.84; dinner: 119.09 ± 16.47 | NR | NR | |||
| Metformin | 46 | Before treatment | 102.15 ± 21.96 | Breakfast: 120.67 ± 24.03; lunch: 120.61 ± 22.63; dinner: 131.22 ± 25.43 | NR | NR | |
| After treatment | 90.09 ± 16.29 | Breakfast: 107.7 ± 16.69; lunch: 106.87 ± 11.16; dinner: 110.76 ± 11.57; p = 0.020 | NR | NR | |||
| Tertti_2013 [38] | Insulin (NPH + lispro + aspart) | 107 | At randomisation | NR | NR | NR | NR | 
| Metformin (23 required additional insulin) | 110 | At randomisation | NR | NR | NR | NR | |
| Delivery | NR | NR | NR | NR | |||
| Niromanesh_2012 [39] | NPH and regular as needed | 80 | First 2 weeks after randomisation | 91.2 ± 7.9 | 114.6 ± 12.1 | NR | NR | 
| Second week after randomisation and until delivery | 86.2 ± 8.7 | 107.6 ± 10.0 | NR | NR | |||
| Randomisation-delivery | 88.7 ± 6.3 | 111.1 ± 9.0 | NR | NR | |||
| Metformin | 80 | First 2 weeks after randomisation | 90.3 ± 9.8; p = 0.529 | 112.2 ± 13.0; p = 0.237 | NR | NR | |
| Second week after randomisation and until delivery | 86.2 ± 8.6; p = 0.985 | 110.4 ± 11.9; p = 0.106 | NR | NR | |||
| 80 | Randomisation-delivery | 88.3 ± 7.7; p = 0.683 | 111.3 ± 9.1; p = 0.870 | NR | NR | ||
| Balaji_2012 [69] | BIAsp 30 | 163 | At enrolment | 103.77 ± 17.94 | NR | NR | 164.66 ± 38.71 | 
| Delivery | 92.97 ± 14.44 | NR | NR | 127.59 ± 28.99 | |||
| BHI 30 | 157 | At enrolment | 108.24 ± 24.88 | NR | NR | 163.83 ± 48.12 | |
| Delivery | 95.43 ± 18.96 | NR | NR | 126.98 ± 29.89 | |||
| Hassan_2012 [40] | Regular and intermediate-acting human insulin | 75 | At enrolment | Median (range): 102.11 (89–110) | NR | NR | Median (range): 236.41 (180–309) | 
| Third trimester/delivery | NR | NR | NR | NR | |||
| Metformin | 75 | At enrolment | Median (range): 100.89 (88–120); p = 0.079 vs. insulin | NR | NR | Median (range): 231.56 (188–280); p = 0.058 vs. insulin | |
| Third trimester/delivery | NR | NR | NR | NR | |||
| Ijas_2011 [41] | Long-(Protaphane) and rapid-(humalog) acting insulin | 50 | At randomisation | 5.4 ± 0.6 mmol | NR | NR | 8.1 ± 1.8 | 
| Metformin | 47 | At randomisation | 5.6 ± 0.9 mmol | NR | NR | 8.2 ± 1.9 | |
| Observational | |||||||
| Han_2020 [72] | Insulin lispro + metformin | 62 | Before treatment | 8 | NR | NR | Breakfast: 13; lunch: 11.8; dinner: 11.8 | 
| After treatment | 5.2 | NR | NR | Breakfast: 7; lunch: 6; dinner: 6 | |||
| Insulin lispro | 55 | Before treatment | 7.9 | NR | NR | Breakfast: 12.8; lunch: 11.8; dinner: 11.8 | |
| After treatment | 7; p < 0.05 vs. insulin + metformin | NR | NR | Breakfast: 9.2, lunch: 8.8, dinner: 9; p < 0.05 vs. insulin + metformin | |||
| Krishnakumar_2020 [73] | Insulin | 37 | Baseline | 103.81 ± 7.98 | 128.30 ± 7.26 | NR | NR | 
| 2 months | 94.59 ± 5.77; p < 0.0001 vs. baseline | 116.05 ± 6.01; p < 0.0001 vs. baseline | NR | NR | |||
| Metformin | 44 | Baseline | 105.16 ± 15.16 | 130.23 ± 16.83 | NR | NR | |
| 2 months | 94.84 ± 6.18; p < 0.0001 vs. baseline | 117.86 ± 6.54; p < 0.0001 vs. baseline | NR | NR | |||
| Rodrigues 2020 [50] | Insulin | 41 | 3rd trimester | NR | NR | NR | NR | 
| Metformin + insulin | 94 | 3rd trimester | NR | NR | NR | NR | |
| Metformin only (subgroup of metformin +) | 77 | 3rd trimester | NR | NR | NR | NR | |
| Zaharieva_2020 [75] | Insulin vs. no insulin | Total-90; insulin n = 34 | NR | 5.2 vs. 4.8; p = 0.0004 | NR | NR | NR | 
| Tang_2019 [31] | Insulin | 180 | NA | Median (IQR): 5.8 (5.5, 6.2) | NR | Median (IQR): 10.2 (9.0, 11.8) | Median (IQR): 8.6 (7.5, 9.3) | 
| MNT | 354 | NA | Median (IQR): 5.3 (5.1, 5.5); p < 0.001 | NR | Median (IQR): 9.5 (8.3, 10.6); p < 0.001 | Median (IQR): 8.3 (7.0, 9.4); p < 0.292 | |
| McGrath_2018 [82] | Insulin (NPH or Levemir and/or NovoRapid) | 83 | At diagnosis | 4.8 | NR | NR | NR | 
| Metformin | 83 | At diagnosis | 4.9 | NR | NR | NR | |
| Diet + lifestyle | 83 | At diagnosis | 4.4; p < 0.001 across treatment arms | NR | NR | NR | |
| Rowan_2018 [85] | Insulin (Adelaide cohort) | 51 | At enrolment | 88 ± 13 | NR | NR | NR | 
| Metformin (Adelaide cohort) | 51 | 36 weeks | NR | NR | NR | NR | |
| Insulin (Auckland cohort) | 58 | At enrolment | 88 ± 16 | NR | NR | NR | |
| Metformin (Auckland cohort) | 58 | 36 weeks | NR | NR | NR | NR | |
| Insulin (Adelaide cohort) | 54 | At enrolment | 90 ± 11 | NR | NR | NR | |
| Metformin (Adelaide cohort) | 54 | 36 weeks | NR | NR | NR | NR | |
| Insulin (Auckland cohort) | 45 | At enrolment | 95 ± 16 | NR | NR | NR | |
| 36 weeks | NR | NR | NR | NR | |||
| Simeonova-Krstevska_2018 [28] | Levemir (detemir) + aspart | 101 | NA | 5.8 ± 1.4; p < 0.05 vs. metformin | 7.9 ± 1.9; p < 0.05 vs. metformin | NR | NR | 
| Metformin | 48 | NA | 5.3 ± 0.7; p = NS vs. diet | 7.0 ± 1.2; p = NS vs. diet | NR | NR | |
| Diet | 200 | NA | 5.1 ± 0.9; p < 0.01 vs. insulin | 6.9 ± 1.6; p < 0.05 vs. insulin | NR | NR | |
| Olmos_2017 [89] | Basal-bolus insulin therapy (BBIT) | 73 | NA | NR | NR | NR | NR | 
| Without BBIT (diet/metformin) | 58 | NA | NR | NR | NR | NR | |
| Xie_2017 [90] | Research arm (insulin aspart intensive treatment/insulin pump) | 45 | NA | 5.2 ± 0.6 | NR | NR | 7.3 ± 1.2 | 
| Reference arm (insulin aspart + detemir) | 45 | NA | 6.8 ± 0.6; p < 0.05 vs. research arm | NR | NR | 8.8 ± 1.2; p < 0.05 vs. research arm | |
| Ito_2016 [92] | RHI or rapid-acting insulin (insulin aspart or lispro) and NPH insulin) | 32 | At diagnosis | 91.5 ± 7.9 | NR | 179.9 ± 34.9 | 150.5 ± 28.5 | 
| 32 | Delivery | 93.2 ± 9.4 | NR | 162.2 ± 41.2 | 124.2 ± 31.4 | ||
| Diet | 70 | At diagnosis | 89.6 ± 8.7; p = 0.313 vs. insulin | NR | 155.3 ± 33.6; p = 0.001 vs. insulin | 135.3 ± 29.7; p = 0.017 vs. insulin | |
| Delivery | 90.8 ± 7.7; p = 0.251 vs. insulin | NR | 142.9 ± 40.7; p = 0.064 vs. insulin | 118.0 ± 29.0; p = 0.410 vs. insulin | |||
| Koren_2016 [55] | Insulin detemir | 29 | NA | 5.1 ± 0.5 | NR | 8 ± 1.3 | 7.78 ± 1.3 | 
| Glyburide | 62 | NA | 5.1 ± 1; p = 0.91 | NR | 7.8 ± 1.3; p = 0.82 | 7.12 ± 1.8; p = 0.13 | |
| Ozgu-Erdinc_2016 [29] | Insulin | 144 | NA | Median (range): 87 (56–275) | NR | Median (max–min): 144 (67–340) | Median (max–min): 132 (53–320) | 
| Diet | 115 | NA | Median (range): 80 (58–157); p < 0.001 | NR | Median (max–min): 137.5 (72–212); p = 0.002 | Median (max–min): 118.5 (72–207); p < 0.001 | |
| Yanagisawa_2016 [30] | Insulin | 36 | NA | OGTT: 88 ± 11 meal TT: 92 ± 16 | NR | OGTT: 177 ± 29; meal TT: 147 ± 32 | OGTT: 161 ± 22; Meal TT: 128 ± 32 | 
| MNT | 77 | NA | OGTT: 83 ± 9; p = 0.013 vs. insulin, meal TT: 84 ± 7; p = 0.014 | NR | OGTT: 173 ± 28; p = NS vs. insulin Meal TT: 121 ± 20 p < 0.001 | OGTT: 157 ± 25; p = NS vs. insulin meal TT: 104 ± 18 p < 0.001 | |
| You_2016 [99] | Regular insulin (NPH if required) | 55 | Baseline | 96.9 ± 15.4 | NR | 200.7 ± 33.9 | 195.9 ± 37.2 | 
| Fast-acting insulin analogues (NPH if required)-aspart or lispro | 142 | Baseline | 99.4 ± 20.5; p = 0.494 | NR | 208.0 ± 36.4; p = 0.194 | 188.8 ± 40.6; p = 0.249 | |
| Benhalima_2015 [32] | Short-acting or long-acting insulin or both | 145 | NA | 97.6 ± 18.8 | NR | 194.7 ± 30.1 | 185.2 ± 28.5 | 
| Diet | 456 | NA | 87.7 ± 10.3; p < 0.0001 vs. insulin | NR | 184.5 ± 25.8; p < 0.0001 vs. insulin | 175.0 ± 22.8; p < 0.0001 vs. insulin | |
| Deepaklal_2014 [100] | Insulin lispro | 201 | At enrolment/first trimester | 99.01 | Post breakfast: 126.9 ± 44.2, post lunch: 125.5 ± 38.3, post dinner: 127.2 ± 38.6 | NR | NR | 
| Delivery | NR | Post breakfast: 106.5 ± 18.8, post lunch: 111 ± 18.4, post dinner: 111.8 ± 19.5 | NR | NR | |||
| Marques_2014 [102] | NPH insulin | 33 | NA | NR | NR | NR | NR | 
| Metformin | 32 | NA | NR | NR | NR | NR | |
| Goh_2011 [109] | Intermediate-acting isophane insulin and short-acting insulin analog | 399 | NA | 5.4 ± 1.1 | NR | NR | 9.9 ± 2.1 | 
| Metformin | 465 | NA | 5.3 ± 0.8 | NR | NR | 9.4 ± 1.6 | |
| Diet | 371 | NA | 4.5 ± 0.7, p < 0.0001 across treatment arms | NR | NR | 9.5 ± 1.1, p = 0.0008 across treatment arms | |
| Flores-Le Roux_2010 [111] | Insulin | 41 | 3rd trimester | NR | NR | NR | NR | 
| Diet | 70 | 3rd trimester | NR | NR | NR | NR | |
| NEF-GDM | 18 | 3rd trimester | NR | NR | NR | NR | |
BBIT basal-bolus insulin therapy, BHI biphasic premixed human insulin, BIAsp biphasic insulin aspart, FBG fasting blood glucose, GDM gestational diabetes mellitus, NA not applicable, NEF no endocrinologic follow-up, NPH neutral protamine Hagedorn, NR not reported, PPG postprandial glucose, RCT randomized controlled trial, RHI regular human insulin, SD standard deviation