Table 1.
Detailed characteristics of all eligible studies.
| References | Year | Population | Single center/ multicenter | Sample size (case/ control) | Characteristics of the participants [%man, age (case/control)] | Duration of treatment | Dose of metformin (mg/d) | Genotyping | Gene (SNPs) | Q-Genie score |
|---|---|---|---|---|---|---|---|---|---|---|
| Cohort study (14) | ||||||||||
| Zhou et al. (10) | 2009 | Chinese | Single center | 1,531 | 59%,59.1 ± 11.2/63.1 ± 10.5 | ≥6 months | NA | TaqMan | SLC22A1:rs12208357, rs72552763 | 51 |
| Tkác et al. (11) | 2013 | Slovakian | Multicenter | 148 | 49%,57.5 ± 0.9 | 6 months | 1,275 | real-time PCR | SLC22A1: rs622342 SLC22A2: rs316019 | 40 |
| Chen (12) | 2014 | Chinese | Single center | 82 | 46.3%,49.80 ± 12.18 | 2 months | 500–1,500 | XP-PCR | SLC22A1: rs628031 rs622342 SLC22A2: rs316019 | 40 |
| Zhou et al. (13) | 2015 | Chinese | Single center | 137 | 50.4%,56.4 ± 11.6 | 3 months | 500–2,000 | TaqMan | SLC22A1:rs1867351, rs4709400, rs628031, rs2297374 | 33 |
| Hou et al. (14) | 2015 | Chinese | Single center | 209 | 57.73%,51.9 ± 12.3(AA)/57.1 ± 7.8(Aa)/49.5 ± 13.3 (aa) | ≥12 months | 1,500 | AS-PCR | SLC22A2: rs316019 | 34 |
| Ghaffari-Cherati et al. (15) | 2016 | Iranian | Single center | 150 | NA,52.7 ± 10.7 | 3 months | 1,000 | PCR-RFLP | SLC22A3: rs3088442 | 32 |
| Liu Zejing et al. (16) | 2016 | Chinese | Single center | 105 | 73.3%,39.2 (35–48) | 3 months | 500 | PCR-RFLP | LC22A1: rs628031 SLC22A4: rs272893 | 31 |
| Fu Ting et al. (17)* | 2016 | Chinese | Single center | 43 | 48.8%,56.25 ± 10.10 | 3 months | 500–2,000 | AS-PCR | SLC22A1: rs628031 rs683369 SLC22A2: rs316019 SLC22A3: rs2048327 | 35 |
| Xiao et al. (18) | 2016 | Chinese | Single center | 53 | 58.5%,49(29-73) | 3 months | 1,000–2,000 | DNA DS | SLC22A1: rs594709 | 45 |
| Hosseyni-Talei (19) | 2017 | Iranian | Single center | 150 | NA,52.7 ± 10.7 | 3 months | 1,000 | PCR-RFLP | SLC22A3: rs2292334 | 32 |
| Mostafa-Hedeab et al. (20) | 2018 | Egyptian | Single center | 100 | NA,40.12 ± 11.46 | NA | NA | TaqMan | SLC22A1: rs12208357 | 32 |
| Reséndiz-Abarca et al. (21) | 2019 | Mexican | Single center | 308 | 46.15% (25–75) | 12 months | NA | TaqMan | SLC22A1: rs622342, rs628031,594709 | 44 |
| Naja et al. (38) | 2019 | Lebanese | Single center | 63 | 58.73%,54.89 ± 6.99 | 6 months | 850 | real-time PCR | SLC22A1: rs622342 | 44 |
| Bao Xuezhi (39) | 2021 | Chinese | Single center | 96 | 68.75%,51.97 ± 10.67/58.17 ± 10.82 | 3 months | 500 | PCR | SLC22A1: rs594709 | 32 |
| Case–Control study (6) | ||||||||||
| Tarasova et al. (22) | 2012 | Latvian | Single center | 246(53/193) | 30.1%,63.8 ± 8.2/58.9 ± 9.9 | NA | ≥500 | TaqMan | SLC22A1: rs12208357, rs34059508, rs628031, rs72552763,rs36056065 SLC22A2: rs316019 | 50 |
| Dujic et al. (23) | 2015 | Bosnia and Herzegovina | Single center | 2,166 (251/1,915) | 58.1%, 67.8 ± 10.5/58.0 ± 10.8 | NA | 1,000 | TaqMan | SLC22A1:rs12208357 rs72552763, rs34130495, rs34059508, rs55918055 | 50 |
| Dujic et al. (24) | 2015 | Bosnia and Herzegovina | Single center | 92 (43/49) | 41.3%, 57.1 ± 9.5/58.8 ± 8.4 | NA | 1,000 | TaqMan | SLC22A1: rs12208357 rs72552763 | 44 |
| Dawed et al. (25) | 2019 | IMI DIRECT cohort | Multicenter | 1,414 (286/1,128) | 57.5%, 60.73 ± 9.84/64.63 ± 9.91 | NA | case: 1,500 (1,000–2,000) control: 1,000 (500–1,000) | PCR-RFLP | SLC22A1: rs12208357, rs72552763, rs34130495 | 54 |
| AL-Eitan et al. (26) | 2019 | Jordanian | Single center | 212 | 38.68%, 56.64 ± 9.4 | ≥6 months | NA | MassARRAY | SLC22A1: rs1867351, rs2282143, rs2282143, rs461473, rs4646272, rs622342, rs683369 SLC22A2: rs10755577, rs17588242,rs17589858 rs2928035, rs3127573, rs316024, rs316025, rs316026, rs533452, rs662301. SLC22A2: rs12194182, rs2292334, rs2504927, rs3123634 | 38 |
| Marta et al. (27) | 2020 | Mexican | Single center | 129 | 29.46%,53.8 ± 11.0 | ≥6 months | NA | TaqMan | SLC22A1: rs72552763 rs622342, rs34059508 rs12208357 SLC22A2: rs316019 | 50 |
| Nested case–control study (8) | ||||||||||
| Umamaheswaran et al. (28) | 2015 | South Indian | Single center | 122 (29/93) | 39%,47.79 ± 10.42/50.12 ± 9.70 | 3 months | 500–2,250 | qRT-PCR | SLC22A1: rs622342 | 33 |
| Mahrooz et al. (29) | 2015 | NA | Single center | 108 (59/49) | 19.4%,53.16 ± 9.7 | 3 months | 1,000 | PCR-RFLP | SLC22A1: rs72552763 | 45 |
| Fu Ting et al. (17)* | 2016 | Chinese | Single enter | 130 | 49.23%,59.00 ± 8.14/55.01 ± 10.68 | 3 months | 500–2,000 | AS-PCR | SLC22A1: rs628031 rs683369 SLC22A2: rs316019 SLC22A3: rs2048327 | 38 |
| Shokri et al. (30) | 2016 | Iranian | Single center | 140 (77/63) | 13.57%,52.96 ± 10.34/53.68 ± 9.68 | 6 months | 1,000 | TaqMan | SLC22A1: rs628031 | 35 |
| Phani et al. (31) | 2018 | South Indian | Multicenter | 188 | 52.13%,57.4 ± 10.6/55.8 ± 11.5 | 3 months | 500–3,000 | PCR-RFLP | SLC22A1: rs622342 SLC22A2: rs316019 | 42 |
| Moeez et al. (32) | 2019 | Pakistani | Multicenter | 600 (300/300) | 48.5%,47.09 ± 12.39/46.99 ± 12.60 | 6 months | NA | AS-PCR | SLC22A3: rs3088442 | 33 |
| Abrahams- October et al. (33) |
2021 | South African | Multicenter | 140 | 31.43%,58.3 ± 11.4/60.7 ± 11.0 | ≥12 months | 1,950 | MassARRAY | SLC22A1: rs622342 rs461473 SLC22A2: rs316009 rs316019 | 36 |
| Taheri et al. (34) | 2022 | Iranian | Single center | 241 (98/102) | 47.5%,56.99 ± 4.85/55.84 ± 4.8 | 6 months | 1,000 | ARMS- PCR | SLC22A3: rs543159 rs1317652 | 40 |
| Cross-sectional study (3) | ||||||||||
| Koshy et al. (35) | 2013 | South Indian | Single center | 60 | NA,35–55 | NA | 500 | TaqMan | SLC22A1: rs12208357 | 29 |
| Kashi et al. (36) | 2015 | Iranian | Single center | 40 | 32.5%,52.35 ± 11.86 | NA | 1,000–1,500 | PCR-RFLP | SLC22A2: rs145450955 | 31 |
| Wu et al. (37) | 2020 | Chinese | Single center | 101 | 60.4%,58.32 ± 10.89/57.07 ± 9.32 | ≥6 months | 1,000–2,500 | Sanger Sequencing | SLC22A1: rs622342 | 41 |
*The investigation conducted by Fu (17) consisted of two parts: One is a cohort design about metformin hypoglycemic effect and the other is a nested case–control design about metformin intolerance.