Neal 2017b.

Study characteristics
Methods	Title: Canagliflozin and cardiovascular and renal events in type 2 diabetes acronym of trial: CANVAS‐R (part of CANVAS program) The CANVAS Program integrated data from two trials; CANVAS and CANVAS‐R study design: Interventional, randomised, parallel assignment, quadruple masking (participant, care provider, investigator, outcomes assessor) total duration of study: 78 weeks number of study centres and location: 667 centres in 30 countries date of study: CANVAS; from December 9, 2009 through February 22, 2017. CANVAS‐R; from January 16, 2014 through February 23, 2017.
Participants	Cardiovascular disease categories: i) intervention: ASCVD: 4127 (71.2%), HF: 803 (13.9%) ii) comparison: ASCVD: 3197 (73.5%), HF: 658 (15.1%) N randomised: i) intervention: 5795, ii) comparison: 4347 N lost to follow‐up/withdrawn: i) intervention: 224, ii) comparison: 184 N analysed: i) intervention: 5795, ii) comparison: 4347 mean age, age range: i) intervention: 63.2 ± 8.3, ii) comparison: 63.4 ± 8.2 gender (female): i) intervention: 2036 (35.1%), ii) comparison: 1597 (36.7%) body mass index (BMI): i) intervention: 31.9 ± 5.9, ii) comparison: 32.0 ± 6.0 diabetes mellitus (DM): (100%) chronic kidney disease (CKD): no data baseline diabetes condition including HbA1c: i) intervention: 8.2 ± 0.9, ii) comparison: 8.2 ± 0.9
Interventions	Intervention: CANVAS; canagliflozin at a dose of 300 mg, or 100 mg. CANVAS‐R; canagliflozin, administered at an initial dose of 100 mg daily with an optional increase to 300 mg starting from week 13; SGLT2i Comparison: placebo (these were each given in addition to standard‐of‐care treatment) Type of active treatment for DM: i) Insulin 2890 (49.9%), SU 2528 (43.6%), Metformin 4447 (76.7%), GLP‐1RA 222 (3.8%), DPP4i 697 (12.0%) ii) Insulin 2205 (50.7%), SU 1833 (42.2%), Metformin 3378 (77.7%), GLP‐1RA 185 (4.3%), DPP4i 564 (13.0%) concomitant medications: i) Statin 4329 (74.7%), Antithrombotic 4233 (73.0%), RAAS inhibitor 4645 (80.2%), BB 3039 (52.4%), Diuretic 2536 (43.8%) ii) Statin 3270 (75.2%), Antithrombotic 3233 (74.4%), RAAS inhibitor 3471 (79.8%), BB 2382 (54.8%), Diuretic 1954 (45.0%)
Outcomes	Primary outcomes: a composite of death from cardiovascular causes, non‐fatal MI, or non‐fatal stroke Secondary outcomes: death from any cause, death from cardiovascular causes, progression of albuminuria, and the composite of death from cardiovascular causes and hospitalisation for HF
Notes	Funding for trial: Funded by AstraZeneca CANVAS and CANVAS‐R ClinicalTrials.gov numbers: NCT01032629 and NCT01989754, respectively
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	”a computer‐generated randomization”
Allocation concealment (selection bias)	Low risk	”Randomization was performed centrally through an interactive Web‐based response system.”
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blinded.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Method of blinding outcomes was not described clearly.
Incomplete outcome data (attrition bias) All outcomes	Low risk	Missing data were unlikely to have an impact on the results of the trial. Dropped out rate was not high (lower than 20%).
Selective reporting (reporting bias)	High risk	Some secondary outcomes were not reported. Change From baseline in Proinsulin/Insulin (PI/I) Ratio at the end of treatment . Change From baseline in Urinary Albumin/Creatinine Ratio at end of treatment .
Other bias	Low risk	There were no other biases.