Results
death, CKD, chronic kidney disease, cancer, Caucasian/White, deaths, Cancer deaths, diabetes
CANCER, EVENT, CERVICAL CANCER, REGRESSION, DIABETES
Of the 2045 participants with diabetes, 965 used metformin at baseline (median [Interquartile range, IQR] follow-up = 4.6 [3.5-5.5] years) and 1080 did not (median [IQR] follow-up = 4.5 [3.3-5.5] years) (Baseline characteristics of ASPREE participants with diabetesMissing data in total cohort (N = 19 114): age at randomization, n = 0; sex, n = 0; ethnicity, n = 0; BMI, n = 89; smoking, n = 0; alcohol use, n = 0; previous regular aspirin use, n = 2; CKD, n = 1350; polypharmacy, n = 0; family cancer history, n = 0; randomized treatment group, n = 0; physical component score of the SF-12, n = 8; personal cancer history, n = 22. Percentages exclude missing values from denominator. Baseline characteristics of participants without diabetes are shown in Ethnicity and race were collected through participant self-report: White/Caucasian or other; “other” consists of Aboriginal/Torres Strait Islanders, American Indian, Asian, Black/African American, Hispanic/Latino or Native Hawaiian/Other Pacific Islander/Maori.Previous regular aspirin use: self-reported regular aspirin use before entering the study.Stage III-V CKD: urine albumin-to- creatinine ratio ≥3 mg/mmol or estimated glomerular filtration rate <60 mL/min/1.73 mFamily cancer history: cancer history in the participant’s blood relatives (mother, father, siblings, and children) self-reported at baseline; ovarian and cervical cancer history were included, which were not included in recent ASPREE publication ( Physical component score: physical component score of the SF-12 quality-of-life questionnaire (IQR; Interquartile Range. 
Nelson-Aalen cumulative-incidence curves (95% confidence interval) for cancer incidence and mortality in people with diabetes by metformin use. Relationship between metformin use and cancer incidence and mortality compared with people with diabetes but no metformin use and those without diabetesNo. = Number of participants with a cancer event. Rate is the event rate per 1000 person-years. BMI = body mass index; CI = confidence interval; CKD = chronic kidney disease; FBGL = fasting blood glucose level; HR = hazard ratio.Adjusted for age at randomization, sex, ethnicity (Caucasian/White vs other, where other includes Aboriginal/Torres Strait Islanders, American Indian, Asian, Black/African American, Hispanic/Latino or Native Hawaiian/Other Pacific Islander/Maori), BMI (as continuous), smoking status (current and former vs never), alcohol status (current and former vs never), previous aspirin use, CKD, treatment group, polypharmacy, family cancer history, physical component summary score, personal cancer history, insulin use, other oral antihyperglycemic medication use, and FBGL.Adjusted for age at randomization, sex, ethnicity (Caucasian/White vs other), BMI (as continuous), smoking status (current and former vs never), alcohol status (current and former vs never), previous aspirin use, CKD, treatment group, polypharmacy, family cancer history, physical component summary score, and personal cancer history. Baseline characteristics of participants without diabetes are shown in Time from randomization to first cancer event.Time from randomization to cancer-related death. This value includes only deaths that were adjudicated to be cancer related. Cancer deaths where the participant did not present with cancer before death were also included (n = 20).The association of metformin with cancer incidence and mortality as well as continuous FBGL measures are shown in Log-adjusted hazard ratios (HRs) (95% confidence interval [CI]) of metformin (vs no metformin) across varying levels of baseline fasting blood glucose. The log-adjusted hazard ratios were determined by using Cox regression models, with an interaction between metformin and blood glucose, adjusting for baseline confounders: age at randomization, sex, ethnicity (Caucasian/White vs other), body mass index (as continuous), smoking status (current and former vs never), alcohol status (current and former vs never), previous aspirin use, chronic kidney disease, treatment group, polypharmacy, family cancer history, physical component summary score, personal cancer history, insulin use, and other oral antihyperglycemic medication use.The combined effect of metformin and aspirin is shown in Effect of metformin and aspirin use on cancer incidence and mortality in those with diabetesUnadjusted because treatment allocation to aspirin or placebo was randomized. CI = confidence interval; HR = hazard ratio.No. = Number of participants with a cancer event. Rate is the event rate per 1000 person-years.Time from randomization to first cancer event.Time from randomization to cancer-related death. This value includes only deaths that were adjudicated to be cancer related.