TABLE 1.
A summary of characteristics of the included studies.
| First author, Year | Study characteristics | Definition of metformin exposure | Follow-up (months) | Adjusting variables | Results | ||||
|---|---|---|---|---|---|---|---|---|---|
| Country | Sample size (met/total) | Design | Stage/Location | Mean or median age (years) | |||||
| Hu et al. (2020) | China | 44/88 | Cohort | OSCC | Mean 53.50 ± 9.53 | Met alone or in combination with other drugs | 60 | Age, gender, urban and rural residence, smoking, alcohol, betel quid chewing, location, TNM stage | RFS:0.42 (0.27–0.64) |
| Lee et al. (2019) | Canada | 195/329 | Cohort | OC, OP, LX | Mean 67.3 ± 9.8 | Taking met at the time of presentation | 37.2 | Primary site, age, treatment modality, extra-capsular spread, perineural invasion, CCI score, smoking, alcohol, Follow-up time, TNM stage | OS:1.04 (0.72–1.5); RFS:1.04 (0.66–1.62); DSS:1.16 (0.68–1.98) |
| Tsou et al. (2019) | China | 49/141 | Cohort | HP | Mean 66.45 | Previous OHA and persisted though the CCRT treatment until the latest follow up | 48 | Age, alcohol, betel nut, cigarette, TNM stage or disease stage | OS: Early stage: 1.54 (0.32–7.22), Late stage: 0.23 (0.08–0.68); DFS: Early stage: 1.44 (0.09–2.14); Late stage: 0.23 (0.07–0.68) |
| Alcusky et al. (2019) | Italy | 708/7,872 | Cohort | NM | Median 68.1 (59.3, 76.7) | Exposed to met after HNC diagnosis | 35.2 | Gender, age, location of residence, mean-centred calendar time in year, TD exposure to chemotherapy indicator, TD exposure to radiation therapy indicator, TD tumor resection indicator, TD diagnosis of regional and metastatic disease indicator, and ECS | OS:0.81 (0.61–1.09) |
| Quimby et al. (2018) | Canada | 165/1,231 | Cohort | NP, HP, LX | Mean 74.55 ± 6.09 | Taking met at the time of diagnosis | 36 | Age, gender, ECS, treatment type, primary site | OS: 1.10 (0.86–1.41); DSS:1.00 (0.70–1.44) |
| Stokes et al. (2018) | United States | 124/1,646 | Cohort | OC, OP and other | >66, Mean 73.99* | Start within 6 months after diagnosis | 24 | Gender, age, race, marital status, SEER registry, population density, TNM stage | OS:0.74 (0.50 1.09); CSS: 0.33 (0.16 0.67) |
| Ogunsakin et al. (2018) | United States | 11/34 | cohort | LX, OP | Not given | Taking met for at least 1 year and at least 1 year after the pathological diagnosis of HNC or death within 1 year after diagnosis, and must take met before death | 60 | Age, primary cancer treatment, race, glucose control, age at death and tumor stage of SCC | OS:0.42 (0.1–1.74) |
| Chang et al. (2017) | China | 39/252 | Cohort | III, IVA, IVB | Mean 56.1 ± 12.2 | Received met at the time of definitive diagnosis of cancer | 24 | Age, gender, disease stage, TNM stage, Eastern Cooperative Oncology Group performance status, CCI, BMI, smoking, alcohol, betel quid chewing | OS:0.79 (0.44–1.42); RFS:1.02 (0.6–1.74) |
| Spratt et al. (2016) | United States | 102/1745 | Cohort | OP | Median 61 (35–79) | From time of diagnosis continued for a minimum of 5 years (or death or last follow-up if less than 5 years) | 60 | Age, gender, primary site of disease, TNM stage, smoking, HPV, P16, dose, chemotherapy | OS:0.73 (0.4–1.33) |
| Kwon et al. (2015) | Korea | 99/1,151 | Cohort | NM | Median 61 (20–80) | 6 months before HNSCC diagnosis through 1 month after diagnosis, and at least 1 month after diagnosis | 65.1 | Patient age and gender, site, TNM stage, smoking status, alcohol, BMI, and initial treatment modalities | OS:0.7 (0.4–1.22); CSS:0.45 (0.20–0.99) |
| Sandulache et al. (2014) | United States | 21/205 | Cohort | LSCC | Mean 64 | Taking metformin during treatment | >36 | Age, gender, race, smoking, alcohol consumption, TNM stage | OS:0.34 (0.12–0.96); DFS:0.50 (0.21–1.22) |
*The mean year was calculated from data.
Abbreviations: met = metformin; OS, overall survival; DFS, disease-free survival; DSS, disease-specific survival; RFS, recurrence-free survival; CSS, cancer-specific survival; OSCC, oral squamous cell carcinoma; OC, oral cavity; OP, oropharynx; LX, larynx; HP, hypopharynx; NP, nasopharynx; NM, not mentioned; LSCC, laryngeal squamous cell carcinoma; HNSCC, head and neck squamous cell carcinoma; TD, time-dependent; CCI, charlson comorbidity index; ECS, elixhauser comorbidity score; NOS, Newcastle-Ottawa Scale.