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1Department of Endocrinology and Metabolism, Hallym University College of Medicine, Chuncheon, Korea
2Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, Gwangju, Korea
3Division of Endocrinology and Metabolism, Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
Copyright © 2021 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
CONFLICTS OF INTEREST
No potential conflict of interest relevant to this article was reported.
AUTHOR CONTRIBUTIONS
Conception or design: S.M., S.H.Y., C.M.O. Acquisition, analysis, or interpretation of data: S.M., J.L., Y.J.K., C.M.O. Drafting the work or revising: S.M., H.S.C., S.H.Y., C.M.O. Final approval of the manuscript: S.M., H.S.C., J.M.Y., S.H.Y., C.M.O.
Study | Study duration and dosage of liraglutide | No. of intervention | No. of control | Diabetes mellitus | Age, yr | Weight, kg | Waist circumference, cm | BMI, kg/m2 | Systolic blood pressure, mm Hg | Diastolic blood pressure, mm Hg | HbA1c, % | LDL-C, mg/dL |
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Ahmadi et al. (2019) [17] | 24 wk | 63 | 59 | 122 (100) | I: 63.8±8.2 | I: 98.8±14.1 | I: 116.1±10.2 | I: 33.7±4.3 | I: 138 (17) | I: 74±13 | I: 8.98±0.99 | I: 86±31 |
1.8 mg/day | C: 63.6±7.7 | C: 99.8±14.8 | C: 115.7±10.6 | C: 33.5±4.0 | C: 134 (14) | C: 75±9 | C: 8.96±1.10 | C: 88±37 | ||||
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Armstrong et al. (2016) [33] | 48 wk | 26 | 26 | 17 (33) | I: 50±11 | I: 101±18 | I: 110±11 | I: 34.2±4.7 | I: 130±13 | I: 79± 11 | I: 5.9±0.7 | I: 100±31 |
1.8 mg/day | C: 52±12 | C: 108±18 | C: 108±18 | C: 37.7±6.2 | C: 133±12 | C: 78± 9 | C: 6.0±0.9 | C: 112±39 | ||||
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Astrup et al. (2009) [31] | 20 wk | 3:93 | 98 | 0 | I | I | NR | I | I | I | NR | I |
1.2–3 mg/day | 1.8:90 | 3: 45.9±10.7 | 3: 97.6±13.7 | 3: 34.8±2.8 | 3: 124±11.3 | 3: 77.8±8.3 | 3: 131±30 | |||||
1.8: 45.5±10.9 | 1.8: 98.0±12.5 | 1.8: 35.0±2.6 | 1.8: 123±13 | 1.8: 77.9±7.9 | 1.8: 137±34 | |||||||
C: 45.9±10.3 | C: 97.3±12.3 | C: 34.9±2.8 | C: 124±11.1 | C: 76.8±8.5 | C: 137±34 | |||||||
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Bensignor et al. (2021) [36] | 52 wk | 66 | 68 | 134 (100) | I: 14.6±1.7 | NR | I: 106.1±20.7 | I: 34.6±10.9 | NR | NR | NR | NR |
0.6 mg–1.8 mg/day | C: 14.6±1.7 | C: 104.3±15.0 | C: 33.3±7.4 | |||||||||
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Blackman et al. (2016) [25] | 32 wk | 180 | 179 | 0 | I: 48.6±9.9 | I: 116.5±23 | I: 122.3±14.5 | I: 38.9±6.4 | I: 126±12 | I: 81±8 | I: 5.7±0.4 | I: 112±29 |
3 mg/day | C: 48.4±9.5 | C: 119±25 | C: 122.7±14.9 | C: 39.4±7.4 | C: 127±12 | C: 82±9 | C: 5.6±0.4 | C: 111±27 | ||||
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Danne et al. (2017) [24] | 5 wk | 14 | 7 | 0 | I: 15.1±0.9 | I: 103.5±12.8 | NR | I: 36.5±3.7 | I: 124±14 | I: 61±9 | I: 5.4±0.3 | NR |
3 mg/day | C: 14.4±1.8 | C: 109.6±30.8 | C: 35.7±5.4 | C: 126±7 | C: 60±6 | C: 5.5±0.3 | ||||||
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Davies et al. (2015) [27] | 56 wk | 3:423 | 212 | 846 (100) | I | I | I | I | I | I | I | I |
1.8 and 3 mg/day | 1.8:211 | 3: 55.0±10.8 | 3: 105.7±21.9 | 3: 118.0±14.4 | 3: 37.1±6.5 | 3: 129±14 | 3: 79±8.6 | 3: 7.9±0.8 | 3: 86.4±36 | |||
1.8: 54.9±10.7 | 1.8: 105.8±21.0 | 1.8: 117.5±14.7 | 1.8: 37.0±6.9 | 1.8: 131±15 | 1.8: 80±9 | 1.8: 8.0±0.8 | 1.8: 92±38.5 | |||||
C: 54.7±9.8 | C: 106.5±21.3 | C: 117.3±14 | C: 37.4±7.1 | C: 129±14 | C: 79.3±10 | C: 7.9±0.8 | C: 85.2±39 | |||||
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de Wit et al. (2016) [29] | 26 wk | 25 | 22 | 47 (100) | NR | NR | I: 110±13 | I: 33.6±6.4 | I: 137±16 | I: 81±6 | NR | NR |
1.8 mg/day | C: 107±15 | C: 31.6±5.1 | C: 141±15 | C: 82±8 | ||||||||
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Frossing et al. (2018) [20] | 26 wk | 48 | 24 | 0 | NR | I: 94.2±15.4 | I: 102.6±10.8 | I: 33.3±5.1 | I: 123±9 | I: 79±8 | I: 5.3 | I: 109±27 |
1.8 mg/day | C: 91.3±13.6 | C: 102.6±11.1 | C: 33.3±4.6 | C: 124±9 | C: 80±7 | C: 5.3 | C: 116±21 | |||||
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Garvey et al. (2020) [10] | 56 wk | 198 | 198 | 396 (100) | I: 55.9±11.3 | I: 100.6±20.8 | I: 114.8±13.7 | I: 35.9±6.5 | I: 129±14 | I: 78±9 | I: 7.9±1.1 | I: 94±33 |
3 mg/day | C: 57.6±10.4 | C: 98.9±19.9 | C: 114.2±13.2 | C: 35.3±5.8 | C: 132±16 | C: 78±9 | C: 8.0±1.0 | C: 94±29 | ||||
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Gudbergsen et al. (2021) [37] | 52 wk | 80 | 76 | NR | I: 59.2±10.8 | I: 96.3±18.2 | I: 105.5±13.9 | I: 32.8±5.5 | NR | NR | NR | NR |
3 mg/day | C: 59.3±9.7 | C: 90±14.3 | C: 101.8±11.1 | C: 31.3±4.0 | ||||||||
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Guo et al. (2020) [38] | 26 wk | 31 | 30 | 61 (100) | I: 53.1±6.3 | I: 84.3±10.8 | I: 95.5±8.0 | I: 29.2±4.2 | NR | NR | I: 7.5±1.3 | I: 127±23 |
1.8 mg/day | C: 52.6±3.9 | C: 82.2±12.4 | C: 82.2±12.4 | C: 28.6 ±3.7 | C: 7.3±1.6 | C: 115±19 | ||||||
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Kelly et al. (2020) [12] | 56 wk | 125 | 126 | NR | I: 14.6±1.6 | I: 99.3±19.7 | I: 104.9±12.7 | I: 35.3±5.1 | I: 116±10 | I: 72±8 | I: 5.3±0.4 | I: 88.6±24 |
3 mg/day | C: 14.5±1.6 | C: 102.2±21.6 | C: 107±13.6 | C: 35.8±5.7 | C: 117±12 | C: 73±8 | C: 5.3±0.4 | C: 86.6±25 | ||||
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Khoo et al. (2019) [16] | 26 wk | 15 | 15 | NR | I: 38.6±8.2 | I: 102.7±16.2 | I: 111.1±10.7 | I: 34.3±3.9 | NR | NR | NR | NR |
3 mg/day | C: 43.6±9.9 | C: 89.6±12.7 | C: 105.8±7.6 | C: 32.2±3.2 | ||||||||
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Kim et al. (2013) [30] | 14 wk | 24 | 27 | 0 | I: 45.2±12.1 | NR | NR | I: 31.9±2.7 | NR | NR | NR | NR |
1.8 mg/day | C: 45.0±12 | C: 31.9±3.5 | ||||||||||
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Kumarathurai et al. (2017) [22] | 12 wk | 27 | 27 | 27 (100) | 61.8±7.6 | 96.9±17.1 | 31.6±4.8 | 31.6±4.8 | 139.3±19.4 | 80.2±10.1 | 6.4±0.5 | 89±27 |
1.8 mg/day | ||||||||||||
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Iacobellis et al. (2017) [23] | 24 wk | 49 | 36 | 85 (100) | I: 50±10 | I: 104.5±22.3 | NR | I: 37.8±7.3 | I: 128±17 | I: 79.5±8 | I: 6.6±0.8 | I: 100±43 |
1.8 mg/day | C: 52±10 | C: 87.3±18.3 | C: 32.6±6.7 | C: 122±13 | C: 77.5±9 | C: 6.4±0.6 | C: 98±31 | |||||
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Larsen et al. (2017) [21] | 66 wk | 47 | 50 | NR | I: 42.1±10.7 | I: 103.3±16.1 | I: 117.3±12.4 | I: 33.7±5.1 | I: 126±11 | I: 84±9.8 | I: 5.6±0.4 | I: 124± 58 |
1.8 mg/day | C: 43.0±10.5 | C: 102.4±23.9 | C: 115.9±15.1 | C: 33.9±6.6 | C: 125±14. | C: 84±7.6 | C: 5.5±0.4 | C: 127±43 | ||||
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Lind et al. (2015) [26] | 24 wk | 63 | 59 | 122 (100) | I: 63.8±8.2 | I: 98.8±14.1 | I: 116.1±10.2 | I: 33.7±4.3 | I: 138±17 | I: 74±13 | I: 8.98±0.99 | I: 86±31 |
1.8 mg/day | C: 63.6±7.7 | C: 99.8±14.8 | C: 115.7±10.6 | C: 33.5±4.0 | C: 134±14 | C: 75±9 | C: 8.96±1.10 | C: 88±37 | ||||
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Nexoe-Larsen et al. (2018) [19] | 12 wk | 26 | 26 | 0 | I: 47.6±10.4 | I: 98.2±17.0 | NR | I: 32.5±3.6 | NR | NR | NR | NR |
3 mg/day | C: 47.5±9.7 | C: 99.8±14.7 | C: 32.6±3.3 | |||||||||
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O’Neil et al. (2018) [18] | 52 wk | 103 | 136 | 0 | I: 49±11 | I: 108.7±21.9 | I: 116.2±13.8 | I: 38.6±6.6 | NR | NR | I: 5.5±0.4 | I: 120 |
3 mg/day | C: 46±13 | C: 114.2±25.4 | C: 119.5±15.9 | C: 40.1±7.2 | C: 5.5±0.4 | C: 120 | ||||||
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Peradze et al. (2019) [15] | 5 wk | 20 | 20 | 3 (15) | NR | NR | NR | I: 35.5±5.8 | NR | NR | NR | I: 52±52 |
3 mg/day | C: 35.1±5.6 | C: 52±52 | ||||||||||
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Pi-Sunyer et al. (2015) [28] | 56 wk | 2,437 | 1,225 | 0 | I: 58±7 | I: 106.2±21.2 | I: 115.0±14.4 | I: 38.3±6.4 | I: 123±12.9 | I: 78.7±8.6 | I: 5.6±0.4 | I: 111.6±27.9 |
3 mg/day | C: 58±8 | C: 106.2±21.7 | C: 114.5±14.3 | C: 38.3±6.3 | C: 123.2±12.8 | C: 78.9±8.5 | C: 5.6±0.4 | C: 112.2±27.6 | ||||
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Tronieri et al. (2020) [40] | 52 wk | 37 | 36 | NR | I: 44.3±11.7 | NR | NR | I: 39.2±5.0 | NR | NR | NR | NR |
3 mg/day | C: 47.4±11.8 | C: 37.6±4.1 | ||||||||||
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van Eyk et al. (2019) [14] | 26 wk | 22 | 25 | 47 (100) | I: 59.9±6.2 | I: 98.4±13.8 | NR | I: 32.6±4.4 | I: | I: | I: 8.3±1.1 | I: 101±33 |
1.8 mg/day | C: 59.2±6.8 | C: 94.5±3.1 | C: 31.6±3.4 | C: | C: | C: 8.1±0.9 | C: 99±35 | |||||
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Vedtofte et al. (2020) [39] | 52 wk | 37 | 45 | 0 | I: 38.8 (34.3–40.7) | I: 89.0 (87.4–107.2) | I: 104 (99–110) | I: 32.1 (27.4–36.3) | I: 125 (121–129) | I: 80 (78–83) | I: 5.1 (5.0–5.3) | I: 127 (93–143) |
1.8 mg/day | C: 38.3 (35.5–41.2) | C: 83.9 (76.3–92.6)0 | C: 104 (101–106) | C: 30.6 (28.4–33.0) | C: 128 (125–132) | C: 82 (79–84) | C: 5.1 (5.0–5.2) | C: 112 (93–135) | ||||
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Wadden et al. (2013) [32] | 56 wk | 207 | 206 | 0 | NR | I: 106.7±22.0 | I: 114.4±15.7 | I: 38.2±6.2 | I: 122.7±13.1 | I: 78.0±8.4 | I: 5.6±0.4 | I: 112±27 |
3 mg/day | C: 105.0±22.5 | C: 112.7±15.2 | C: 37.5±6.2 | C: 123.2±12.3 | C: 79.2±7.5 | C: 5.5±0.4 | C: 116±31 | |||||
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Wadden et al. (2019) [13] | 52 wk | 50 | 50 | 0 | I: 45.2±12.3 | I: 107.8±17.9 | I: 116.7±10.4 | I: 38.5±5.4 | I: 135±12 | I: 74±7 | I: 5.7±0.3 | I: 112±30 |
3 mg/day | C: 49.5±11.0 | C: 105.8±14.7 | C: 116.7±11.6 | C: 38.0±4.3 | C: 139±14 | C: 78±10 | C: 5.6±0.3 | C: 117±30 | ||||
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Wadden et al. (2020) [11] | 56 wk | 142 | 140 | 0 | I: 45.4±11.6 | I: 108.5±22.1 | I: 116±14.4 | I: 39.3±6.8 | I: 125±15 | I: 80±9 | I: 5.5±0.4 | I: 112±31 |
3 mg/day | C: 49±11.2 | C: 106.7±22 | C: 115±15.6 | C: 38.7±7.2 | C: 127±14 | C: 81±8 | C: 5.5±0.4 | C: 120±35 | ||||
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Wang et al. (2020) [35] | 16 wk | 14 | 16 | 0 | I: 36.4±8.9 | NR | NR | I: 37.0±4.3 | NR | NR | NR | NR |
3 mg/day | C: 35.7±11.0 | C: 38.4±5.7 | ||||||||||
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Whicher et al. (2021) [34] | 26 wk | 24 | 23 | 4 (8) | I: 42.7±11.3 | I: 111.4±25.5 | I: 123.8±20.1 | I: 37.5±6.9 | I: 130±24 | I: 92±23 | I: 5.5±0.6 | I: 120±11 |
3 mg/day | C: 45.4±10.7 | C: 117.7±23.5 | C: 130.6±14.0 | C: 41.0±6.7 | C: 134±15 | C: 93±7 | C: 5.8±0.5 | C: 104±31 |
Dosage of liraglutide outcome | 1.8 mg/day | 3.0 mg/day | ||||
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No. | MD (95% CI, I2) | Reference | No. | MD (95% CI, I2) | Reference | |
Weight, kg | 10 | −4.04 (−4.61 to −3.47, 0%) | [14,17,20–22,30,31,33,38,39] | 12 | −4.24 (−5.27 to −3.22, 75.4%) | [12,13,16–19,24,25,28,31,32,34] |
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BMI, kg/m2 | 11 | −1.38 (−1.60 to −1.16, 14.2%) | [14,17,20,21,23,27,29,33,36,38,39] | 11 | −1.66 (−1.92 to −1.39, 73.1%) | [12,13,16,18,25,27,28,32,34,35,37] |
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Waist circumference, cm | 10 | −2.55 (−3.21 to −1.89, 0%) | [17,20,21,27,29,30,33,36,38,39] | 12 | −3.39 (−3.93 to −2.85, 30.5%) | [10–13,16,18,25,27,28,34,37] |
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Blood pressure, mm Hg | ||||||
Systolic blood pressure | 11 | −2.73 (−4.03 to −1.42, 0%) | [20–23,26,27,29–31,33,34,39] | 12 | −2.87 (−3.42 to −2.33, 0%) | [10–13,18,24,25,27,28,31,32,34] |
Diastolic blood pressure | 11 | −0.30 (−1.21 to 0.62, 0%) | [20–23,26,27,29–31,33,39] | 12 | −0.73 (−1.12 to −0.34, 0%) | [10–13,18,24,25,27,28,31,32,34] |
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HbA1c, % | 11 | −0.61 (−0.83 to −0.38, 92.1%) | [14,20–23,26,27,29,33,38,39] | 10 | −0.27 (−0.36 to −0.18, 93.3%) | [10–13,18,24,25,27,28,32] |
Dosage of liraglutide outcome | Without DM | With DM | ||||
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No. | MD (95% CI, I2) | Reference | No. | MD (95% CI, I2) | Reference | |
Weight, kg | 10 | −4.47 (−5.38 to −3.56, 69.7%) | [13,18–20,24,25,28,30–32] | 4 | −3.78 (−4.68 to −3.23, 0%) | [14,17,22,38] |
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BMI, kg/m2 | 7 | −1.88 (−2.05 to −1.72, 29.6%) | [13,18,20,25,28,32,35] | 7 | −1.32 (−1.53 to −1.12, 10.2%) | [14,17,23,27,29,38] |
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Waist circumference, cm | 8 | −3.96 (−4.37 to −3.54, 0%) | [11,13,18,20,25,28,30,32] | 6 | −2.61 (−3.14 to −2.07, 0%) | [10,17,27,29,36,38] |
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Blood pressure, mm Hg | ||||||
Systolic blood pressure | 10 | −2.82 (−3.41 to −2.34, 0%) | [11,13,18,20,24,25,28,30–32] | 6 | −3.20 (−4.39 to −2.01, 0%) | [10,22,23,26,27,29] |
Diastolic blood pressure | 10 | −0.82 (−1.25 to −0.40, 0%) | [11,13,18,20,24,25,28,30–32] | 6 | −0.56 (−1.34 to 0.21, 0%) | [10,22,23,26,27,29] |
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HbA1c, % | 8 | −0.20 (−0.25 to −0.14, 72.4%) | [11,13,18,20,24,25,28,32] | 8 | −0.73 (−0.89 to −0.58, 73.2%) | [10,14,22,23,26,27,29,38] |
Adverse event | Prevalence of adverse event | Odds ratio (95% CI) | Heterogeneity (I2), % | Reference | |
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Liraglutide | Placebo | ||||
Serious adverse events | 6.1 (279/4,587) | 5.6 (155/2,759) | 1.10 (0.89–1.36) | 0 | [10–13,18,19,21,23–28,31,33,34,36–38] |
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Treatment withdrawal due to adverse events | 9.0 (429/4,777) | 3.6 (106/2,916) | 2.44 (1.95–3.06) | 0 | [1,10–13,16,18–20,23–26,29–31,33,36,37,41] |
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Gastrointestinal adverse events | 67.4 (1,368/2,031) | 43.9 (639/1,454) | 2.99 (2.57–3.47) | 48.8 | [10–13,18,19,24–26,30,31,33,38,41] |
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Nausea | 39.4 (1,849/4,689) | 14.2 (406/2,859) | 4.00 (3.53–4.53) | 41.1 | [1,10–13,15,16,18,20,21,25,26,30–33,36,41] |
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Diarrhea | 20.4 (958/4,689) | 10.9 (312/2,859) | 2.13 (1.85–2.46) | 0 | [1,10–13,15,16,18,20,21,25,26,30–33,36,41] |
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Vomiting | 16.1 (741/4,610) | 4.6 (127/2,785) | 4.03 (3.30–4.93) | 12.4 | [1,10–13,15,18,20,21,25,30–33,36,41] |
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Abdominal pain | 6.8 (277/4,071) | 4.7 (111/2,387) | 1.62 (1.28–2.06) | 43.9 | [1,10–13,15,16,20,21,30,32,33,36,41] |
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Hypoglycemia | 36.7 (478/1,303) | 26.0 (237/910) | 1.66 (1.32–2.09) | 38.6 | [10,11,18,21,24,32,36] |