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©The Author(s) 2022.
World J Cardiol. Nov 26, 2022; 14(11): 599-616
Published online Nov 26, 2022. doi: 10.4330/wjc.v14.i11.599
Published online Nov 26, 2022. doi: 10.4330/wjc.v14.i11.599
Table 1 Jadad score of included studies
| Ref. | Randomization | Blinding | Accountability | Jadad score |
| Bailey et al[24], 2015 | 2 | 1 | 1 | 4 |
| Bailey et al[25], 2013 | 1 | 1 | 1 | 3 |
| Rosenstock et al[26], 2012 | 1 | 1 | 1 | 3 |
| Wilding et al[27], 2014 | 2 | 2 | 1 | 5 |
| Matthaei et al[34], 2015 | 2 | 1 | 1 | 4 |
| Jabbour et al[30], 2014 | 1 | 1 | 1 | 3 |
| Anker et al[15], 2021 | 2 | 2 | 1 | 5 |
| Sone et al[36], 2020 | 2 | 1 | 1 | 4 |
| Bolinder et al[33], 2014 | 2 | 2 | 1 | 5 |
| Rosenstock et al[37], 2015 | 2 | 1 | 1 | 4 |
| Rosenstock et al[38], 2014 | 2 | 1 | 1 | 4 |
| Kohan et al[28], 2016 | 1 | 1 | 1 | 3 |
| Zinman et al[5], 2015 | 2 | 1 | 1 | 3 |
| Brown et al[35], 2020 | 1 | 1 | 1 | 3 |
| Qin et al[32], 2019 | 1 | U | U | 1 |
| Gause-Nilsson 20141 | 1 | U | U | 1 |
| List et al[39], 2009 | 1 | 1 | 1 | 3 |
| McMurray et al[31], 2019 | 2 | 2 | 1 | 5 |
Table 2 Characteristics of included studies
| Treatment group | Placebo group | Participants (n) | Mean age (yr) | Race (n) | |||||||||
| Ref. | Duration (wk) | %male | %DM | SGLT2-I | Other therapy | Other therapy | SGLT2-I | Placebo | SGLT2-I | Placebo | White | Asian | Black |
| Bailey et al[25], 2013 | 102 | 100% | DAPA (2.5) | Metformin | Metformin | 137 | 137 | 55.0 (9.3) | 53.7 (10.3) | ||||
| DAPA (5) | Metformin | 137 | 54.3 (9.4) | ||||||||||
| DAPA (10) | Metformin | 135 | 52.7 (9.9) | ||||||||||
| Bailey et al[24], 2015 | 102 | 100% | DAPA (2.5) | Metformin | Metformin | 65 | 75 | 53.0 (11.7) | 52.7 (10.3) | ||||
| DAPA (5) | Metformin | 64 | 52.6 (10.9) | ||||||||||
| DAPA (10) | Metformin | 70 | 50.6 (10.0) | ||||||||||
| Bolinder et al[33], 2014 | 102 | 55.6% | 100% | DAPA (10) | Placebo only | 69 | 71 | 60.6 (8.2) | 60.8 (6.9) | 140 | NR | NR | |
| Brown et al[35], 2020 | 52 | 57.6% | 100% | DAPA (10) | Placebo only | 32 | 34 | 64.25 (7.01) | 66.74 (6.62) | ||||
| Gause-Nilsson 20141 | 104 | 100% | DAPA (10) | Insulin | Insulin | 480 | 482 | ||||||
| Jabbour et al[30], 2014 | 48 | 54.8% | 100% | DAPA (10) | Sitagliptin, metformin | Sitagliptin, metformin | 223 | 224 | 54.8 (10.4) | 55.0 (10.2) | 332 | 4 | 17 |
| Zinman et al[5], 2015 | 102 | DAPA (2.5) | Placebo only | 625 | 785 | 57.5 (9.9) | 56.9 (10.2) | ||||||
| DAPA (5) | 767 | 56.5 (10.1) | |||||||||||
| DAPA (10) | 859 | 56.0 (9.9) | |||||||||||
| List et al[39], 2009 | 12 | 100% | DAPA (2.5) | Placebo only | 59 | 54 | 55 (11) | 53 (11) | |||||
| DAPA (5) | Metformin | 58 | 56 | 55 (12) | 54 (9) | ||||||||
| DAPA (10) | 47 | 54 (9) | |||||||||||
| DAPA (20) | 59 | 55 (10) | |||||||||||
| DAPA (50) | 56 | 53 (10) | |||||||||||
| Matthaei et al[34], 2015 | 52 | 49.2% | 100% | DAPA (10) | Placebo only | 108 | 108 | 61.1 (9.7) | 60.9 (9.2) | 206 | NR | NR | |
| McMurray et al[31], 2019 | 72 | 77% | 45% | DAPA (10) | Placebo only | 2373 | 2371 | 66.2 (11.0) | 66.5 (10.8) | 3333 | 1116 | 226 | |
| Qin et al[32], 2019 | 16 | 100% | DAPA (10) | Placebo only | 22 | 12 | |||||||
| DAPA (10) | Saxagliptin | 22 | |||||||||||
| Rosenstock et al[26], 2012 | 48 | 100% | DAPA (5) | Pioglitazone | Pioglitazone | 141 | 139 | 53.2 (10.9) | 53.5 (11.4) | ||||
| DAPA (10) | Pioglitazone | 140 | 53.8 (10.4) | ||||||||||
| Wilding et al[27], 2014 | 104 | 100% | DAPA (2.5) | Insulin, existing OAD | Insulin, existing OAD | 202 | 193 | 59.8 (7.6) | 58.8 (8.6) | ||||
| DAPA (5/10)2 | Insulin, existing OAD | 211 | 59.3 (7.9) | ||||||||||
| DAPA (10) | Insulin, existing OAD | 194 | 59.3 (8.8) | ||||||||||
| Anker et al[15], 2021 | 112 | 55% | 49% | EMPA (10) | Placebo only | 2997 | 2991 | 71.8 (9.3) | 71.9 (9.6) | 4542 | 824 | 258 | |
| Sone et al[36], 2020 | 52 | 72.6% | 100% | EMPA (10) | Placebo only | 86 | 90 | 58.3 (10.0) | 59.1 (10.7) | NR | 266 | NR | |
| EMPA (25) | 90 | 58.6 (9.5) | |||||||||||
| Rosenstock et al[37], 2015 | 78 | 56% | 100% | EMPA (10) | Placebo only | 169 | 170 | 58.6 (9.8) | 58.1 (9.4) | 343 | 98 | 48 | |
| EMPA (25) | 155 | 59.9 (10.5) | |||||||||||
| Rosenstock et al[38], 2014 | 52 | 45% | 100% | EMPA (10) | Placebo only | 186 | 188 | 56.7 (8.7) | 55.3 (10.1) | 531 | NR | 19 | |
| EMPA (25) | 189 | 58.0 (9.4) | |||||||||||
| Zinman et al[5], 2015 | 220 | 71.5% | 100% | EMPA (10) | Placebo only | 2345 | 2333 | 63.0 (8.6) | 63.2 (8.8) | 5081 | 1517 | 357 | |
| EMPA (25) | 2342 | 63.2 (8.6) | |||||||||||
Table 3 Baseline values for the MetS components
| Waist circumference (cm) | Triglyceride (mg/dL) | HDL (mg/dL) | SBP (mmHg) | DBP (mmHg) | Fasting plasma glucose | ||||||||
| Ref. | SGLT2-I (daily dose, mg) | SGLT2-I | Placebo | SGLT2-I | Placebo | SGLT2-I | Placebo | SGLT2-I | Placebo | SGLT2-I | Placebo | SGLT2-I | Placebo |
| Bailey et al[25], 2013 | DAPA (2.5) | 126.6 (14.5) | 127.7 (14.6) | 79.5 (8.7) | 80.9 (9.0) | 161.3 ± 43 | 165.42 (46.44) | ||||||
| DAPA (5) | 126.9 (14.3) | 80.8 (8.5) | 169.0 ± 49 | ||||||||||
| DAPA (10) | 126.0 (15.9) | 79.0 (10.2) | 155.9 ± 38.7 | ||||||||||
| Bailey et al[24], 2015 | DAPA (2.5) | 105.6 (14.9) | 103.2 (13.8) | 129.3 (16.1) | 124.7 (16.3) | 79.1 (7.9) | 81.0 (9.5) | 163.8 ± 48.6 | 160.2 (41.4) | ||||
| DAPA (5) | 104.3 (11.7) | 124.7 (15.3) | 81.6 (8.9) | 162 ± 45 | |||||||||
| DAPA (10) | 108.1 (13.2) | 125.1 (16.4) | 80.2 (8.6) | 167.4 ± 41.4 | |||||||||
| Bolinder et al[33], 2014 | DAPA (10) | 105.6 ± 10.1 | 104.5 ± 12.3 | 136.1 ± 13.8 | 133.3 ± 13.7 | 80.6 ± 8.0 | 80.4 ± 8.3 | 147.6 ± 25.2 | 149.4 ± 25.2 | ||||
| Brown et al[35], 2020 | DAPA (10) | 137.25 ± 7.5 | 136.15 ± 9.11 | 79.16 ± 8.63 | 77.79 ± 8.25 | 140.4 ± 63 | 144.9 ± 54.0 | ||||||
| Jabbour et al[30], 2014 | DAPA (10) | 162.2 (36.8) | 163.0 (34.5) | ||||||||||
| Kohan et al[28], 2016 | DAPA (2.5) | 133.1 (17.2) | 130.8 (15.8) | 79.8 (9.3) | 79.6 (9.0) | ||||||||
| DAPA (5) | 130.5 (16.2) | 79.5 (8.9) | |||||||||||
| DAPA (10) | 131.1 (16.3) | 79.1 (9.3) | |||||||||||
| List et al[39], 2009 | DAPA (2.5) | 127 ± 14 | 126 ± 16 | 78 ± 8 | 77 ± 8 | 145 ± 34 | 150 ± 46 | ||||||
| DAPA (5) | 126 ± 13 | 126 ± 13 | 76 ± 8 | 78 ± 8 | 153 ± 48 | 143 ± 33 | |||||||
| DAPA (10) | 127 ± 16 | 77 ± 8 | 148 ± 38 | ||||||||||
| DAPA (20) | 127 ± 15 | 77 ± 8 | 149 ± 41 | ||||||||||
| DAPA (50) | 126 ± 16 | 77 ± 9 | 153 ± 42 | ||||||||||
| Matthaei et al[34], 2015 | DAPA (10) | 185.9 ± 123.9 | 177.1 ± 79.7 | 46.44 ± 11.6 | 46.4 ± 11.6 | 134.5 ± 12.6 | 136.4 ± 14.2 | 80.4 ± 9.2 | 81.6 ± 7.9 | 167.4 ± 43.3 | 180.2 ± 43.1 | ||
| McMurray et al[31], 2019 | DAPA (10) | 72.5 ± 13.2 | |||||||||||
| Rosenstock et al[26], 2012 | DAPA (5) | 168.6 +/-52.1 | 160.7 +/-47.0 | ||||||||||
| DAPA (10) | 164.9 +/-46.3 | ||||||||||||
| Wilding et al[27], 2014 | DAPA (2.5) | 109.7 (13.4) | 110.2 (14.5) | 180 ± 59.4 | 171 (57.6) | ||||||||
| DAPA (5/10)1 | 109.3 (13.4) | 185.4 ± 59.4 | |||||||||||
| DAPA (10) | 109.6 (12.5) | 172.8 ± 54 | |||||||||||
| Anker et al[15], 2021 | EMPA (10) | 131.8 ± 15.6 | 131.9 ± 15.7 | 78 | |||||||||
| Rosenstock et al[37], 2015 | EMPA (10) | 175.23 ± 14.2 | 158.5 ± 7.97 | 46.1 ± 0.77 | 46 ± 0.77 | 132.4 ± 15.5 | 133.9 ± 16.3 | 78.4 ± 9.2 | 78.6 ± 10.9 | 138.6 ± 52.2 | 142.2 ± 46.8 | ||
| EMPA (25) | 162.8 ± 0.8 | 46.1 ± 0.78 | 132.8 ± 15.1 | 77.9 ± 10.2 | 145.8 ± 25 | ||||||||
| Rosenstock et al[38], 2014 | EMPA (10) | 171.7 ± 8.85 | 178.9 ± 12.4 | 46.1 ± 0.79 | 45.2 ± 0.77 | 134.2 ± 16.4 | 132.6 ± 15.8 | 79.5 ± 8.5 | 78.2 ± 8.8 | 158.9 ± 46.8 | 151.38 ± 45.72 | ||
| EMPA (25) | 169.9 ± 7.08 | 46.4 ± 0.77 | 132.9 ± 14.2 | 78.7 ± 8.5 | 149.2 ± 48.6 | ||||||||
| Sone et al[36], 2020 | EMPA (10) | 93.3 ± 8.8 | 93.8 ± 9.6 | 134.2 ± 14.6 | 135.7 ± 14.0 | 80.1 ± 10.2 | 79.6 ± 8.7 | 168.8 ± 43.1 | 159.1 ± 38.5 | ||||
| EMPA (25) | 93.1 ± 8.3 | 136.3 ± 14.3 | 80.0 ± 10.6 | 156.1 ± 37.7 | |||||||||
| Zinman et al[5], 2015 | EMPA (10) | 104.9 | 105.1 | 168.4 ± 2.67 | 170.7 ± 2.53 | 44.7 ± 0.25 | 44.0 ± 0.24 | 134.9 ± 16.8 | 135.8 ± 17.2 | 76.6 ± 9.8 | 76.8 ± 10.1 | ||
| EMPA (25) | 104.9 | 172.6 ± 2.27 | 44.5 ± 0.25 | 135.6 ± 17.0 | 76.6 ± 9.7 | ||||||||
Table 4 Baseline data for HbA1C, BW, and UA
| Body weight (kg) | Hemoglobin A1c (%) | Uric acid (mg/dL) | |||||
| Ref. | SGLT2-I (daily dose, mg) | SGLT2-I | Placebo | SGLT2-I | Placebo | SGLT2-I | Placebo |
| Bailey et al[25], 2013 | DAPA (2.5) | 84.90 (17.77) | 87.74 (19.24) | 7.99 (0.90) | 8.12 (0.96) | ||
| DAPA (5) | 84.73 (16.26) | 8.17 (0.96) | |||||
| DAPA (10) | 86.28 (17.53) | 7.92 (0.82) | |||||
| Bailey et al[24], 2015 | DAPA (2.5) | 90.8 (22.8) | 88.8 (19.0) | 7.92 (0.90) | 7.84 (0.87) | 5.92 (1.42) | 5.09 (1.32) |
| DAPA (5) | 87.6 (17.1) | 7.86 (0.94) | 5.55 (1.44) | ||||
| DAPA (10) | 94.2 (18.7) | 8.01 (0.96) | 5.67 (1.44) | ||||
| Bolinder et al[33], 2014 | DAPA (10) | 92.1 (14.1) | 90.9 (13.7) | 7.19 (0.44) | 7.16 (0.53) | ||
| Brown et al[35], 2020 | DAPA (10) | 91.58 (14.62) | 91.48 (14.13) | 7.8 (3.17) | 7.66 (3.08) | ||
| Jabbour et al[30], 2014 | DAPA (10) | 91.0 (21.6) | 89.2 (20.9) | 7.9 (0.8) | 8.0 (0.8) | ||
| Kohan et al[28], 2016 | DAPA (2.5) | 8.17 (0.86) | 8.12 (0.92) | ||||
| DAPA (5) | 8.27 (0.95) | ||||||
| DAPA (10) | 8.11 (0.93) | ||||||
| List et al[39], 2009 | DAPA (2.5) | 90 (20) | 89 (18) | 7.6 (0.7) | 7.9 (0.9) | 5.5 (1.2) | 5.5 (1.4) |
| DAPA (5) | 89 (17) | 8.0 (0.9) | 5.2 (1.3) | ||||
| DAPA (10) | 86 (17) | 8.0 (0.8) | 5.5 (1.2) | ||||
| DAPA (20) | 88 (18) | 7.7 (0.9) | 5.3 (1.3) | ||||
| DAPA (50) | 92 (19) | 7.8 (1.0) | 5.6 (1.4) | ||||
| Matthaei et al[34], 2015 | DAPA (10) | 88.6 (17.6) | 90.1 (16.2) | 8.08 (0.91) | 8.24 (0.87) | ||
| Rosenstock et al[26], 2012 | DAPA (5) | 87.8 (20.7) | 86.4 (21.3) | 8.40 (1.03) | 8.34 (1.00) | ||
| DAPA (10) | 84.8 (22.2) | 8.37 (0.96) | |||||
| Wilding et al[27], 2014 | DAPA (2.5) | 93.0 (16.7) | 94.5 (19.8) | 8.46 (0.78) | 8.47 (0.77) | ||
| DAPA (5/10)1 | 93.3 (17.4) | 8.62 (0.89) | |||||
| DAPA (10) | 94.5 (16.8) | 8.57 (0.82) | |||||
| Anker et al[15], 2021 | EMPA (10) | ||||||
| Sone et al[36], 2020 | EMPA (10) | 73.3 (11.5) | 74.0 (11.3) | 8.8 (0.7) | 8.7 (0.7) | ||
| EMPA (25) | 72.2 (11.4) | 8.7 (0.7) | |||||
| Rosenstock et al[37], 2015 | EMPA (10) | 91.6 (20.1) | 90.5 (22.5) | 8.3 (0.8) | 8.2 (0.8) | 5.26 (1.71) | 5.5 (2.1) |
| EMPA (25) | 94.7 (20.7) | 8.3 (0.8) | 5.63 (2) | ||||
| Rosenstock et al[38], 2014 | EMPA (10) | 96.7 (17.9) | 95.5 (17.5) | 8.39 (0.74) | 8.33 (0.72) | 5.48 (2.13) | 5.5 (2.0) |
| EMPA (25) | 95.9 (17.3) | 8.29 (0.72) | 5.56 (2.07) | ||||
| Zinman et al[5], 2015 | EMPA (10) | 85.9 (18.8) | 86.6 (19.1) | 8.07 (0.86) | 8.08 (0.84) | 5.9 | 6 |
| EMPA (25) | 86.5 (19.0) | 8.06 (0.84) | 5.98 | ||||
- Citation: Olagunju A, Yamani N, Kenny D, Mookadam M, Mookadam F, Unzek S. Potential for sodium-glucose cotransporter-2 inhibitors in the management of metabolic syndrome: A systematic review and meta-analysis. World J Cardiol 2022; 14(11): 599-616
- URL: https://www.wjgnet.com/1949-8462/full/v14/i11/599.htm
- DOI: https://dx.doi.org/10.4330/wjc.v14.i11.599