Bhatt 2021.

Study characteristics
Methods	Title: Sotagliflozin in patients with diabetes and recent worsening heart failure acronym of trial: SOLOIST‐WHF study design: a phase 3, double‐blind, randomised, placebo‐controlled trial total duration of study: the median duration of follow‐up was 9.2 months, the median duration of treatment was 7.8 months details of any 'run‐in' period: unknown number of study centres and location: 466 locations study setting: outpatients date of study: from 11 June 2018 to 5 June 2020
Participants	Cardiovascular disease categories: HF: 100%, HF: ischaemic 712 (58.6%), ASCVD: 712 (58.6%) N randomised: i) intervention: 608, ii) comparison:614 N lost to follow‐up/withdrawn: i) intervention: 20 (3.3%), ii) comparison: 23 (3.7%) N analysed: i) intervention: 608, ii) comparison: 614 mean age, age range: i) intervention: 69 (63‐76), ii) comparison: 70 (64‐76) gender (female): i) intervention: 198 (32.6%), ii) comparison: 214 (34.9%) body mass index (BMI): BMI, kg/m2; (< 30): 558, (≥ 30) 661 diabetes mellitus (DM): (100%) chronic kidney disease (CKD): eGFR < 60 ml/min/1.73 m2 : 854 (69.9%) severity of condition (such as the commonly‐used classification system, NYHA classification or the ACC/AHA stages of heart failure): NYHA Class; I: 31, II: 552, III: 560, IV: 54 left ventricular ejection fraction: i) intervention: 35 (28‐47) %, ii) comparison: 35 (28‐45) % baseline diabetes condition including HbA1c: i) intervention: 7.1 (6.4‐8.3), ii) comparison: 7.2 (6.4‐8.2) smoking history: NA
Interventions	Intervention: 200 mg of sotagliflozin once daily (with a dose increase to 400 mg, depending on side effects); SGLT2i Comparison: placebo Type of active treatment for DM: i) intervention: Any glucose‐lowering medication: 522 (85.9%), Metformin 320 (52.6%), SU 114 (18.8%), DPP4i 96 (15.8%), Insulin 217 (35.7%), GLP‐1RA 17 (2.8%) ii) comparison: Any glucose‐lowering medication: 522 (85.0%), Metformin 320 (52.1%), SU 114 (18.6%), DPP4i inhibitor 102(16.6%), Insulin 217 (35.3%), GLP‐1RA 23 (3.7%) concomitant medications: i) intervention: ACEi 254, ARB 245, ARNI 93, MRA 403, BB 564, Loop 580, other diuretic 66 ii) comparison: ACEi 241, ARB 270, ARNI 112, MRA 385, BB 561, Loop 581, other diuretic 62
Outcomes	Primary outcomes: total number of deaths from cardiovascular causes and hospitalizations and urgent visits for heart failure (first and subsequent) Secondary outcomes: total number of hospitalisations and urgent visits for heart failure; the incidence of death from cardiovascular causes; the incidence of death from any cause; the total number of deaths from cardiovascular causes, hospitalizations for heart failure, nonfatal myocardial infarctions, and nonfatal strokes; the total number of deaths from cardiovascular causes, hospitalizations and urgent visits for heart failure, and events of heart failure during hospitalization; the change in score on the Kansas City Cardiomyopathy Questionnaire‐12 item (KCCQ‐12; scores range from 0 to 100, with higher scores indicating better quality of life) to month 4; and the change in the estimated GFR
Notes	Funding for trial: Sanofi and Lexicon Pharmaceuticals NCT03521934
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation was performed centrally with the use of interactive‐response technology and was stratified according to left ventricular ejection fraction (< 50% or ≥ 50%) and geographic region of enrolment (North America, Latin America, western Europe, eastern Europe, or rest of the world) at baseline.
Allocation concealment (selection bias)	Low risk	Randomisation was performed centrally, with the use of interactive‐response technology.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blind.
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. Drop‐out rate was not high (lower than 20%).
Selective reporting (reporting bias)	High risk	Several secondary and other endpoints were not presented in the report; Time to first occurrence of the composite of positively adjudicated sustained ≥ 50% decrease in eGFR from baseline (for ≥ 30 days), chronic dialysis, renal transplant, or positively adjudicated sustained eGFR < 15 mL/min/1.73 m2 (for ≥ 30 days) in the total patient population Proportion of patients with HHF or urgent HF visit within 30 days of randomisation Time to ≥ 50% decrease in eGFR from baseline Proportion of patients with ≥ 1 new onset of atrial fibrillation, atrial flutter, or ventricular arrhythmia from randomisation Time to first MI (fatal) Time to first stroke (fatal) Changes from baseline to Month 1 and Month 4 for NT‐proBNP Changes from baseline in loop diuretics Changes in haemoconcentration from baseline at Week 2, Month 1, Month 4, Month 12, and EOT Changes from baseline to Month 4, Month 12, and Month 24 in: ‐ Haemoglobin A1c ‐ Body weight
Other bias	Low risk	There were no other biases.