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1Department of Endocrinology, Mymensingh Medical College, Mymensingh, Bangladesh
2Department of Medicine, Army Medical College Cumilla, Cumilla, Bangladesh
3Department of Endocrinology, CEDAR Superspeciality Clinics, New Delhi, India
4Department of Endocrinology, National Hospital of Sri Lanka, Colombo, Sri Lanka
5Department of Obstetrics and Gynecology, Atpara Upazila Health Complex, Netrokona, Bangladesh
6Department of Endocrinology, JSS Medical College, JSS Academy of Higher Education and Research, Mysore, India
Copyright © 2025 Korean Endocrine Society
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://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: A.B.M.K.H., D.D. Acquisition, analysis, or interpretation of data: A.B.M.K.H., M.S.A., T.S., F.T.Z.A., L.N. Drafting the work or revising: A.B.M.K.H., M.S.A., D.D., T.S., F.T.Z.A., L.N. Final approval of the manuscript: A. B.M.K.H., M.S.A., D.D., T.S., F.T.Z.A., L.N.
Registration no., Phase, Place of the trial | Trial ID (name), Study | Major characteristics of the study subjects | Study arms | Number | Age, yr, mean±SD | Female sex, % | Duration, wk |
---|---|---|---|---|---|---|---|
NCT03131687, Phase 2, Multicenter in Poland, Puerto Rico, Slovakia, and USA | Frias et al. (2018) [25] | Adults with T2D on diet and exercise (±metformin), HbA1c 7%–10.5%, BMI 23–50 kg/m2 | Tirzepatide 1 mg | 52 | 57.4±8.9 | 44 | 26 |
Tirzepatide 5 mg | 55 | 57.9±8.2 | 38 | ||||
Tirzepatide 10 mg | 51 | 56.5±9.9 | 41 | ||||
Tirzepatide 15 mg | 53 | 56.0±7.6 | 59 | ||||
Placebo | 51 | 56.6±8.9 | 56 | ||||
Dulaglutide 1.5 mg | 54 | 58.7±7.8 | 43 | ||||
NCT04184622, Phase 3, Multicenter in multiple countries | SURMOUNT-1, Jastreboff et al. (2022) [26] | Adults with BMI 30 or 27 kg/m2 and at least one weight-related complication, excluding diabetes | Tirzepatide 5 mg | 630 | 45.6±12.7 | 67.6 | 72 |
Tirzepatide 10 mg | 636 | 44.7±12.4 | 67.1 | ||||
Tirzepatide 15 mg | 630 | 44.9±12.3 | 67.5 | ||||
Placebo | 642 | 44.4±12.5 | 67.8 | ||||
NCT04657003, Phase 3, Multicenter in multiple countries | SURMOUNT-2, Garvey et al. (2023) [27] | Adults with T2D, BMI 27 kg/m2, HbA1c 7%–10% | Tirzepatide 10 mg | 312 | 54.3±10.7 | 51 | 72 |
Tirzepatide 15 mg | 311 | 53.6±10.6 | 51 | ||||
Placebo | 315 | 54.7±10.5 | 50 | ||||
NCT04657016, Phase 3, Multicenter in USA, Argentina, and Brazi l | SURMOUNT-3, Wadden et al. (2023) [28] | Adults with BMI 30 or 27 kg/m2 and at least one weight-related complication, excluding diabetes | Tirzepatide MTD (10 or 15 mg)a | 287 | 45.4±12.6 | 63.1 | 72 |
Placebo | 292 | 45.7±11.8 | 62.7 | ||||
NCT05024032, Phase 3, Multicenter in China | SURMOUNT-CN, Zhao et al. (2024) [29] | Adults with BMI 28 or 24 kg/m2 and at least one weight-related comorbidity, excluding diabetes | Tirzepatide 10 mg | 70 | 34.7±7.2 | 50 | 52 |
Tirzepatide 15 mg | 71 | 35.8±9.3 | 49.3 | ||||
Placebo | 69 | 37.8±10.2 | 47.8 | ||||
NCT03861052, NCT04093752, Phase 3, Multicenter in Japan | SURPASS J-mono, Inagaki et al. (2022) [30] | Age 20 years with T2D on diet and exercise or discontinued OAD monotherapy, HbA1c 7%–10%, BMI 23 kg/m2 | Tirzepatide 5 mg | 159 | 56.8±10.1 | 29 | 52 |
Tirzepatide 10 mg | 158 | 56.2±10.3 | 25 | ||||
Tirzepatide 15 mg | 160 | 56.0±10.7 | 18 | ||||
Dulaglutide 0.75 mg | 159 | 57.5±10.2 | 26 | ||||
NCT03954834, Phase 3, Multicenter in India, Japan, Mexico, and USA | SURPASS-1, Rosenstock et al. (2021) [31] | Adults with T2D inadequately controlled with diet and exercise alone and who were naive to injectable diabetes therapy, HbA1c 7%–9.5%, BMI 23 kg/m2 | Tirzepatide 5 mg | 121 | 54.1±11.9 | 54 | 40 |
Tirzepatide 10 mg | 121 | 55.8±10.4 | 40 | ||||
Tirzepatide 15 mg | 121 | 52.9±12.3 | 48 | ||||
Placebo | 115 | 53.6±12.8 | 51 | ||||
NCT03987919, Phase 3, Multicenter in multiple countries | SURPASS-2, Frias et al. (2021) [32] | Adults with T2D inadequately controlled with metformin, HbA1c 7%–10.5%, BMI 25 kg/m2 | Tirzepatide 5 mg | 470 | 56.3±10.0 | 56.4 | 40 |
Tirzepatide 10 mg | 469 | 57.2±10.5 | 49.3 | ||||
Tirzepatide 15 mg | 470 | 55.9±10.4 | 54.5 | ||||
Semaglutide | 469 | 56.9±10.8 | 52.0 | ||||
NCT03882970, Phase 3, Multicenter in multiple countries | SURPASS-3, Ludvik et al. (2021) [33] | Adults with T2D treated with any combination of metformin, SU, or SGLT2i, HbA1c 7%–10.5%, BMI 25 kg/m2 | Tirzepatide 5 mg | 358 | 57.2±10.1 | 44 | 52 |
Tirzepatide 10 mg | 360 | 57.4±9.7 | 46 | ||||
Tirzepatide 15 mg | 359 | 57.5±10.2 | 46 | ||||
Insulin degludec | 360 | 57.5±10.1 | 41 | ||||
NCT03730662, Phase 3, Multicenter in multiple countries | SURPASS-4, Del Prato et al. (2021) [34] | Adults with T2D inadequately controlled with metformin ±an SGLT2i, HbA1c 7%–10.5%, BMI 25 kg/m2 | Tirzepatide 5 mg | 329 | 62.9±8.6 | 40 | 52 |
Tirzepatide 10 mg | 328 | 63.7±8.7 | 36 | ||||
Tirzepatide 15 mg | 338 | 63.7±8.6 | 40 | ||||
Insulin glargine | 1,000 | 63.8±8.5 | 36 | ||||
NCT04039503, Phase 3, Multicenter in multiple countries | SURPASS-5, Dahl et al. (2022) [35] | Adults with T2D receiving stable doses of once-daily insulin glargine ±metformin, HbA1c 7%–10.5%, BMI 23 kg/m2 | Tirzepatide 5 mg | 116 | 62±10 | 47 | 40 |
Tirzepatide 10 mg | 119 | 60±10 | 39 | ||||
Tirzepatide 15 mg | 120 | 61±10 | 46 | ||||
Placebo | 120 | 60±10 | 45 | ||||
NCT04537923, Phase 3b, Multicenter in multiple countries | SURPASS-6, Rosenstock et al. (2023) [36] | Adults with T2D inadequately controlled with basal insulin ±up to two OADs, HbA1c 7.5%–11%, BMI 23–45 kg/m2 | Tirzepatide 5 mg | 243 | 58.0±10.2 | 56.4 | 52 |
Tirzepatide 10 mg | 238 | 59.6±9.4 | 62.6 | ||||
Tirzepatide 15 mg | 236 | 58.2±9.6 | 59.3 | ||||
Insulin lispro | 708 | 59.0±9.7 | 55.9 | ||||
NCT04093752, Phase 3, Multicenter in China, South Korea, Australia, and India | SURPASS-AP-Combo, Gao et al. (2023) [37] | Adults with T2D inadequately controlled with metformin ±SU, HbA1c 7.5%–11%, BMI 23 kg/m2 | Tirzepatide 5 mg | 230 | 53.1±11.2 | 41.7 | 40 |
Tirzepatide 10 mg | 228 | 53.5±11.1 | 44.7 | ||||
Tirzepatide 15 mg | 229 | 54.3±11.6 | 43.7 | ||||
Insulin glargine | 220 | 55.6±11.4 | 46.4 |
Registration no., Phase, Place of the trial | Trial ID (name), Study | Major characteristics of the study subjects | Study arms | Number | Age, yr, mean±SD | Female sex, % | Duration, wk |
---|---|---|---|---|---|---|---|
NCT03131687, Phase 2, Multicenter in Poland, Puerto Rico, Slovakia, and USA | Frias et al. (2018) [25] | Adults with T2D on diet and exercise (±metformin), HbA1c 7%–10.5%, BMI 23–50 kg/m2 | Tirzepatide 1 mg | 52 | 57.4±8.9 | 44 | 26 |
Tirzepatide 5 mg | 55 | 57.9±8.2 | 38 | ||||
Tirzepatide 10 mg | 51 | 56.5±9.9 | 41 | ||||
Tirzepatide 15 mg | 53 | 56.0±7.6 | 59 | ||||
Placebo | 51 | 56.6±8.9 | 56 | ||||
Dulaglutide 1.5 mg | 54 | 58.7±7.8 | 43 | ||||
NCT04184622, Phase 3, Multicenter in multiple countries | SURMOUNT-1, Jastreboff et al. (2022) [26] | Adults with BMI 30 or 27 kg/m2 and at least one weight-related complication, excluding diabetes | Tirzepatide 5 mg | 630 | 45.6±12.7 | 67.6 | 72 |
Tirzepatide 10 mg | 636 | 44.7±12.4 | 67.1 | ||||
Tirzepatide 15 mg | 630 | 44.9±12.3 | 67.5 | ||||
Placebo | 642 | 44.4±12.5 | 67.8 | ||||
NCT04657003, Phase 3, Multicenter in multiple countries | SURMOUNT-2, Garvey et al. (2023) [27] | Adults with T2D, BMI 27 kg/m2, HbA1c 7%–10% | Tirzepatide 10 mg | 312 | 54.3±10.7 | 51 | 72 |
Tirzepatide 15 mg | 311 | 53.6±10.6 | 51 | ||||
Placebo | 315 | 54.7±10.5 | 50 | ||||
NCT04657016, Phase 3, Multicenter in USA, Argentina, and Brazi l | SURMOUNT-3, Wadden et al. (2023) [28] | Adults with BMI 30 or 27 kg/m2 and at least one weight-related complication, excluding diabetes | Tirzepatide MTD (10 or 15 mg) |
287 | 45.4±12.6 | 63.1 | 72 |
Placebo | 292 | 45.7±11.8 | 62.7 | ||||
NCT05024032, Phase 3, Multicenter in China | SURMOUNT-CN, Zhao et al. (2024) [29] | Adults with BMI 28 or 24 kg/m2 and at least one weight-related comorbidity, excluding diabetes | Tirzepatide 10 mg | 70 | 34.7±7.2 | 50 | 52 |
Tirzepatide 15 mg | 71 | 35.8±9.3 | 49.3 | ||||
Placebo | 69 | 37.8±10.2 | 47.8 | ||||
NCT03861052, NCT04093752, Phase 3, Multicenter in Japan | SURPASS J-mono, Inagaki et al. (2022) [30] | Age 20 years with T2D on diet and exercise or discontinued OAD monotherapy, HbA1c 7%–10%, BMI 23 kg/m2 | Tirzepatide 5 mg | 159 | 56.8±10.1 | 29 | 52 |
Tirzepatide 10 mg | 158 | 56.2±10.3 | 25 | ||||
Tirzepatide 15 mg | 160 | 56.0±10.7 | 18 | ||||
Dulaglutide 0.75 mg | 159 | 57.5±10.2 | 26 | ||||
NCT03954834, Phase 3, Multicenter in India, Japan, Mexico, and USA | SURPASS-1, Rosenstock et al. (2021) [31] | Adults with T2D inadequately controlled with diet and exercise alone and who were naive to injectable diabetes therapy, HbA1c 7%–9.5%, BMI 23 kg/m2 | Tirzepatide 5 mg | 121 | 54.1±11.9 | 54 | 40 |
Tirzepatide 10 mg | 121 | 55.8±10.4 | 40 | ||||
Tirzepatide 15 mg | 121 | 52.9±12.3 | 48 | ||||
Placebo | 115 | 53.6±12.8 | 51 | ||||
NCT03987919, Phase 3, Multicenter in multiple countries | SURPASS-2, Frias et al. (2021) [32] | Adults with T2D inadequately controlled with metformin, HbA1c 7%–10.5%, BMI 25 kg/m2 | Tirzepatide 5 mg | 470 | 56.3±10.0 | 56.4 | 40 |
Tirzepatide 10 mg | 469 | 57.2±10.5 | 49.3 | ||||
Tirzepatide 15 mg | 470 | 55.9±10.4 | 54.5 | ||||
Semaglutide | 469 | 56.9±10.8 | 52.0 | ||||
NCT03882970, Phase 3, Multicenter in multiple countries | SURPASS-3, Ludvik et al. (2021) [33] | Adults with T2D treated with any combination of metformin, SU, or SGLT2i, HbA1c 7%–10.5%, BMI 25 kg/m2 | Tirzepatide 5 mg | 358 | 57.2±10.1 | 44 | 52 |
Tirzepatide 10 mg | 360 | 57.4±9.7 | 46 | ||||
Tirzepatide 15 mg | 359 | 57.5±10.2 | 46 | ||||
Insulin degludec | 360 | 57.5±10.1 | 41 | ||||
NCT03730662, Phase 3, Multicenter in multiple countries | SURPASS-4, Del Prato et al. (2021) [34] | Adults with T2D inadequately controlled with metformin ±an SGLT2i, HbA1c 7%–10.5%, BMI 25 kg/m2 | Tirzepatide 5 mg | 329 | 62.9±8.6 | 40 | 52 |
Tirzepatide 10 mg | 328 | 63.7±8.7 | 36 | ||||
Tirzepatide 15 mg | 338 | 63.7±8.6 | 40 | ||||
Insulin glargine | 1,000 | 63.8±8.5 | 36 | ||||
NCT04039503, Phase 3, Multicenter in multiple countries | SURPASS-5, Dahl et al. (2022) [35] | Adults with T2D receiving stable doses of once-daily insulin glargine ±metformin, HbA1c 7%–10.5%, BMI 23 kg/m2 | Tirzepatide 5 mg | 116 | 62±10 | 47 | 40 |
Tirzepatide 10 mg | 119 | 60±10 | 39 | ||||
Tirzepatide 15 mg | 120 | 61±10 | 46 | ||||
Placebo | 120 | 60±10 | 45 | ||||
NCT04537923, Phase 3b, Multicenter in multiple countries | SURPASS-6, Rosenstock et al. (2023) [36] | Adults with T2D inadequately controlled with basal insulin ±up to two OADs, HbA1c 7.5%–11%, BMI 23–45 kg/m2 | Tirzepatide 5 mg | 243 | 58.0±10.2 | 56.4 | 52 |
Tirzepatide 10 mg | 238 | 59.6±9.4 | 62.6 | ||||
Tirzepatide 15 mg | 236 | 58.2±9.6 | 59.3 | ||||
Insulin lispro | 708 | 59.0±9.7 | 55.9 | ||||
NCT04093752, Phase 3, Multicenter in China, South Korea, Australia, and India | SURPASS-AP-Combo, Gao et al. (2023) [37] | Adults with T2D inadequately controlled with metformin ±SU, HbA1c 7.5%–11%, BMI 23 kg/m2 | Tirzepatide 5 mg | 230 | 53.1±11.2 | 41.7 | 40 |
Tirzepatide 10 mg | 228 | 53.5±11.1 | 44.7 | ||||
Tirzepatide 15 mg | 229 | 54.3±11.6 | 43.7 | ||||
Insulin glargine | 220 | 55.6±11.4 | 46.4 |
Control Group | Tirzepatide dose | No. of participants with outcome/participants analyzed |
Pooled effect size, RR (95% CI) | I2, % | P value | |
---|---|---|---|---|---|---|
Tirzepatide arm | Control arm | |||||
Placebo | All doses (pooled) | 32/3,824 | 21/1,605 | 0.66 (0.38–1.16) | 0 | 0.15 |
5 mg | 13/922 | 11/929 | 1.20 (0.54–2.66) | 0 | 0.65 | |
10 mg | 5/1,309 | 18/1,313 | 0.34 (0.13–0.86) | 0 | 0.02 | |
15 mg | 14/1,593 | 21/1,605 | 0.72 (0.37–1.40) | 0 | 0.33 | |
Insulin | All doses (pooled) | 32/3,476 | 24/2,288 | 0.89 (0.49–1.60) | 0 | 0.69 |
5 mg | 10/1,160 | 24/2,288 | 1.00 (0.45–2.24) | 0 | 1.00 | |
10 mg | 13/1,154 | 24/2,288 | 1.23 (0.57–2.65) | 0 | 0.59 | |
15 mg | 9/1,162 | 24/2,288 | 0.89 (0.38–2.10) | 0 | 0.79 | |
GLP-1RA | All doses (pooled) | 10/2,045 | 3/682 | 0.97 (0.22–4.34) | 17 | 0.97 |
5 mg | 5/684 | 3/682 | 1.50 (0.20–11.43) | 37 | 0.70 | |
10 mg | 4/678 | 3/682 | 1.32 (0.29–6.00) | 0 | 0.72 | |
15 mg | 1/683 | 3/682 | 0.48 (0.06–3.69) | 0 | 0.48 |
Outcome variable | Control group | No. of participants with outcome/participants analyzed |
Pooled effect size, RR (95% CI) | I2, % | P value | |
---|---|---|---|---|---|---|
Tirzepatide arm | Control arm | |||||
Breast cancer | All (pooled) | 7/6,346 | 6/3,346 | 0.59 (0.21–1.65) | 0 | 0.31 |
Placebo | 2/3,161 | 4/1,370 | 0.30 (0.07–1.30) | 0 | 0.11 | |
Insulin | 5/3,185 | 2/1,976 | 1.13 (0.27–4.81) | 0 | 0.87 | |
Cholangiocarcinoma | All (pooled) | 1/2,435 | 2/1,475 | 0.33 (0.05–2.08) | 0 | 0.24 |
Insulin | 1/2,072 | 1/1,360 | 0.58 (0.06–5.57) | 0 | 0.64 | |
Colon cancer | All (pooled) | 8/5,871 | 5/3,187 | 0.73 (0.26–2.04) | 0 | 0.54 |
Placebo | 2/986 | 2/430 | 0.41 (0.06–2.78) | 0 | 0.36 | |
Insulin | 3/3,476 | 3/2,288 | 0.91 (0.24–3.43) | 0 | 0.89 | |
Gastric cancer | All (pooled) | 2/1,700 | 0/675 | 1.24 (0.13–11.86) | 0 | 0.85 |
Glioblastoma | All (pooled) | 1/3,131 | 2/2,177 | 0.48 (0.08–3.04) | 0 | 0.44 |
Insulin | 0/1,712 | 2/1,708 | 0.33 (0.03–3.19) | 0 | 0.34 | |
Lung cancer | All (pooled) | 4/6,730 | 8/3,444 | 0.39 (0.12–1.20) | 0 | 0.10 |
Placebo | 1/2,055 | 1/694 | 0.33 (0.03–3.16) | 0 | 0.34 | |
Insulin | 2/2,789 | 6/2,068 | 0.38 (0.08–1.87) | 0 | 0.23 | |
GLP-1RA | 1/2,045 | 1/682 | 0.33 (0.03–3.20) | 0 | 0.34 | |
Lymphoma (any) | All (pooled) | 0/3,027 | 3/1,784 | 0.18 (0.03–1.17) | 0 | 0.07 |
Meningioma | All (pooled) | 3/3,578 | 2/1,863 | 0.62 (0.12–3.20) | 0 | 0.57 |
Insulin | 1/1,682 | 1/1,220 | 0.57 (0.06–5.46) | 0 | 0.62 | |
Ovarian cancer | All (pooled) | 2/2,350 | 1/1,020 | 0.68 (0.11–4.32) | 1 | 0.68 |
Insulin | 2/1,072 | 0/584 | 1.65 (0.17–15.86) | 0 | 0.66 | |
Pancreatic cancer | All (pooled) | 3/3,731 | 1/1,917 | 0.85 (0.10–7.43) | 30 | 0.89 |
Placebo | 1/2,259 | 1/758 | 0.33 (0.03–3.16) | 0 | 0.34 | |
Prostate cancer | All (pooled) | 5/1,898 | 5/1,116 | 0.53 (0.14–1.91) | 0 | 0.33 |
Placebo | 2/924 | 1/363 | 0.64 (0.08–5.21) | 0 | 0.68 | |
Renal cancer | All (pooled) | 8/5,419 | 1/2,683 | 1.33 (0.37–4.78) | 0 | 0.66 |
Placebo | 3/2,538 | 1/1,055 | 0.86 (0.12–6.09) | 15 | 0.88 | |
GLP-1RA | 2/1,886 | 0/628 | 1.00 (0.10–9.61) | 0 | 1.00 | |
Skin cancer | All (pooled) | 5/4,669 | 0/1,764 | 1.52 (0.31–7.34) | 0 | 0.61 |
Placebo | 3/2,183 | 0/935 | 2.24 (0.25–20.25) | 0 | 0.47 | |
Squamous cell carcinoma | All (pooled) | 3/3,481 | 0/1,829 | 1.45 (0.23–9.17) | 0 | 0.70 |
Insulin | 2/2,072 | 0/1,360 | 1.74 (0.18–16.71) | 0 | 0.63 | |
Thyroid cancer (papillary) | All (pooled) | 5/3,011 | 1/1,224 | 1.07 (0.22–5.12) | 0 | 0.93 |
Placebo | 2/2,324 | 1/1,004 | 0.80 (0.11–5.67) | 11 | 0.82 | |
Urinary bladder cancer | All (pooled) | 1/2,359 | 2/1,652 | 0.49 (0.07–3.27) | 6 | 0.46 |
Insulin | 0/2,072 | 2/1,360 | 0.19 (0.02–1.86) | 0 | 0.15 | |
Uterine cancer | All (pooled) | 4/2,504 | 0/893 | 1.12 (0.23–5.53) | 0 | 0.89 |
Placebo | 3/1,752 | 0/649 | 1.17 (0.19–7.41) | 0 | 0.87 |
Section and topic | Item # | Checklist item | Location where item is reported |
---|---|---|---|
Title | |||
Title | 1 | Identify the report as a systematic review. | Page 1 |
Abstract | |||
Abstract | 2 | See the PRISMA 2020 for abstracts checklist. | Page 3 |
Introduction | |||
Rationale | 3 | Describe the rationale for the review in the context of existing knowledge. | Page 5,6 |
Objectives | 4 | Provide an explicit statement of the objective(s) or question(s) the review addresses. | Page 6 |
Methods | |||
Eligibility criteria | 5 | Specify the inclusion and exclusion criteria for the review and how studies were grouped for the syntheses. | Page 7,8 |
Information sources | 6 | Specify all databases, registers, websites, organisations, reference lists and other sources searched or consulted to identify studies. Specify the date when each source was last searched or consulted. | Page 7 |
Search strategy | 7 | Present the full search strategies for all databases, registers and websites, including any filters and limits used. | Page 7 |
Selection process | 8 | Specify the methods used to decide whether a study met the inclusion criteria of the review, including how many reviewers screened each record and each report retrieved, whether they worked independently, and if applicable, details of automation tools used in the process. | Page 7,8 |
Data collection process | 9 | Specify the methods used to collect data from reports, including how many reviewers collected data from each report, whether they worked independently, any processes for obtaining or confirming data from study investigators, and if applicable, details of automation tools used in the process. | Page 8 |
Data items | 10a | List and define all outcomes for which data were sought. Specify whether all results that were compatible with each outcome domain in each study were sought (e.g., for all measures, time points, analyses), and if not, the methods used to decide which results to collect. | Page 8 |
10b | List and define all other variables for which data were sought (e.g., participant and intervention characteristics, funding sources). Describe any assumptions made about any missing or unclear information. | Page 8 | |
Study risk of bias assessment | 11 | Specify the methods used to assess risk of bias in the included studies, including details of the tool(s) used, how many reviewers assessed each study and whether they worked independently, and if applicable, details of automation tools used in the process. | Page 8 |
Effect measures | 12 | Specify for each outcome the effect measure(s) (e.g., risk ratio, mean difference) used in the synthesis or presentation of results. | Page 8 |
Synthesis methods | 13a | Describe the processes used to decide which studies were eligible for each synthesis (e.g., tabulating the study intervention characteristics and comparing against the planned groups for each synthesis [item #5]). | Page 8,9 |
13b | Describe any methods required to prepare the data for presentation or synthesis, such as handling of missing summary statistics, or data conversions. | Page 8 | |
13c | Describe any methods used to tabulate or visually display results of individual studies and syntheses. | Page 9 | |
13d | Describe any methods used to synthesize results and provide a rationale for the choice(s). If meta-analysis was performed, describe the model(s), method(s) to identify the presence and extent of statistical heterogeneity, and software package(s) used | Page 9 | |
13e | Describe any methods used to explore possible causes of heterogeneity among study results (e.g., subgroup analysis, meta-regression). | Page 9 | |
13f | Describe any sensitivity analyses conducted to assess robustness of the synthesized results. | Page 9 | |
Reporting bias assessment | 14 | Describe any methods used to assess risk of bias due to missing results in a synthesis (arising from reporting biases). | Page 8 |
Certainty assessment | 15 | Describe any methods used to assess certainty (or confidence) in the body of evidence for an outcome. | Page 9 |
Results | |||
Study selection | 16a | Describe the results of the search and selection process, from the number of records identified in the search to the number of studies included in the review, ideally using a flow diagram. | Page 10 |
16b | Cite studies that might appear to meet the inclusion criteria, but which were excluded, and explain why they were excluded. | Page 10 | |
Study characteristics | 17 | Cite each included study and present its characteristics. | Page 10 |
Risk of bias in studies | 18 | Present assessments of risk of bias for each included study. | Page 11 |
Results of individual studies | 19 | For all outcomes, present, for each study: (a) summary statistics for each group (where appropriate) and (b) an effect estimate and its precision (e.g. confidence/credible interval), ideally using structured tables or plots. | Pages 11,12,13 |
Results of syntheses | 20a | For each synthesis, briefly summarise the characteristics and risk of bias among contributing studies. | Pages 11,12,13 |
20b | Present results of all statistical syntheses conducted. If meta-analysis was done, present for each the summary estimate and its precision (e.g., confidence/credible interval) and measures of statistical heterogeneity. If comparing groups, describe the direction of the effect. | Pages 11,12,13 | |
20c | Present results of all investigations of possible causes of heterogeneity among study results. | Pages 11,12,13 | |
20d | Present results of all sensitivity analyses conducted to assess the robustness of the synthesized results. | Pages 11,12,13 | |
Reporting biases | 21 | Present assessments of risk of bias due to missing results (arising from reporting biases) for each synthesis assessed. | Pages 11,12,13 |
Certainty of evidence | 22 | Present assessments of certainty (or confidence) in the body of evidence for each outcome assessed. | Pages 11,12,13 |
Discussion | |||
Discussion | 23a | Provide a general interpretation of the results in the context of other evidence. | Pages 13,14,15 |
23b | Discuss any limitations of the evidence included in the review. | Page 15,16 | |
23c | Discuss any limitations of the review processes used. | Page 15,16 | |
23d | Discuss implications of the results for practice, policy, and future research. | Page 15,16 | |
Other information | |||
Registration and protocol | 24a | Provide registration information for the review, including register name and registration number, or state that the review was not registered. | Page 7 |
24b | Indicate where the review protocol can be accessed, or state that a protocol was not prepared. | Page 7 | |
24c | Describe and explain any amendments to information provided at registration or in the protocol. | Not applicable | |
Support | 25 | Describe sources of financial or non-financial support for the review, and the role of the funders or sponsors in the review. | Title page |
Competing interests | 26 | Declare any competing interests of review authors. | Title page |
Availability of data, code and other materials | 27 | Report which of the following are publicly available and where they can be found: template data collection forms; data extracted from included studies; data used for all analyses; analytic code; any other materials used in the review. | Title page |
SD, standard deviation; T2D, type 2 diabetes; HbA1c, glycated hemoglobin; BMI, body mass index; MTD, maximum tolerated dose; OAD, oral anti-diabetic drugs; SU, sulfonylureas; SGLT2i, sodium-glucose cotransporter-2 inhibitor. Tirzepatide MTD was analyzed as tirzepatide 15 mg.
RR, risk ratio; CI, confidence interval; GLP-1RA, glucagon-like peptide-1 receptor agonist.
RR, risk ratio; CI, confidence interval; GLP-1RA, glucagon-like peptide-1 receptor agonist.
PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.