Table 1: Results from landmark cardiovascular outcome trials with SGLT2 inhibitors.

Study	Type of subjects, number, median follow-up	Drug and dosage	CV outcomes	Renal outcomes
EMPA-REG OUTCOME48 (NCT01131676)	T2DM N=7,020 3.1 years	Empagliflozin 10 mg or 25 mg versus placebo, once daily	PEP: CV death, non-fatal MI, or non-fatal stroke, 0.86 (0.74–0.99); NI p<0.001, superiority p=0.04 All-cause mortality: 0.68 (0.57–0.82)* CV death: 0.62 (0.49–0.77)* HHF: 0.65 (0.50–0.85)* HHF or CV death: 0.66 (0.55–0.79)* MI (fatal or non-fatal): 0.87 (0.70–1.09) Stroke (fatal or non-fatal): 1.18 (0.89–1.56)	EMPA-REG (renal analysis)39 Incident or worsening nephropathy: 0.61 (0.53–0.70) Progression to macroalbuminuria: 0.62 (0.54–0.72) Doubling of serum creatinine†: 0.56 (0.39–0.79) Initiation of renal-replacement therapy: 0.45 (0.21–0.97) Worsening of nephropathy‡: 0.54 (0.40–0.75)
CANVAS45§ (NCT01032629)	T2DM N=10,142 3.6 years	Canagliflozin 100 mg or 300 mg versus placebo, daily	PEP: CV death, non-fatal MI, or non-fatal stroke, 0.86 (0.75–0.97); NI p<0.001, superiority p=0.02 CV death: 0.87 (0.72–1.06) HHF: 0.67 (0.52–0.87) All-cause mortality: 0.87 (0.74–1.01) MI (fatal or non-fatal): 0.89 (0.73–1.09) Stroke (fatal or non-fatal): 0.87 (0.69–1.09)	Progression of albuminuria: 0.73 (0.67–0.79)* Worsening of nephropathy‡: 0.60 (0.47–0.77)*
CREDENCE51 (NCT02065791)	T2DM and albuminuric CKD N=4,401 2.6 years	Canagliflozin 100 mg versus placebo, daily	CV death, MI or stroke: 0.80 (0.67–0.95)* CV death or HHF: 0.69 (0.57–0.83)* All-cause mortality: 0.83 (0.68–1.02) CV death, MI, stroke, HHF or UA: 0.74 (0.63–0.86) HHF: 0.61 (0.47–0.80)*	PEP: 0.70 (0.59–0.82)* Worsening of nephropathy‡: 0.66 (0.53–0.81)* ESKD: 0.68 (0.54–0.86)*
DECLARE-TIMI 5852 (NCT01730534)	T2DM N=17,160 4.2 years	Dapagliflozin 10 mg versus placebo, daily	PEP: CV death, non-fatal MI, or non-fatal stroke, 0.93 (0.84–1.03); NI p<0.001, superiority p=0.17 CV death: 0.98 (0.82–1.17) CV death or HHF: 0.83 (0.73–0.95)* All-cause mortality: 0.93 (0.82–1.04) HHF: 0.73 (0.61–0.88)* MI (fatal or non-fatal): 0.89 (0.77–1.01) Stroke (fatal or non-fatal): 1.01 (0.84–1.21)	Worsening of nephropathy‡: 0.76 (0.67–0.87)
DAPA-HF14 (NCT03036124)	HFrEF with and without T2DM N=4,744 18.2 months	Dapagliflozin 10 mg versus placebo, daily	Composite of HHF or CV death or urgent heart failure visit: 0.74 (0.65–0.85)* HHF: 0.70 (0.59–0.83)* CV death: 0.82 (0.69–0.98)* All-cause death: 0.83 (0.71–0.97)* in HFrEF patients with and without T2DM

Outcomes reported as HR (95% CI).

*Significant.

†Accompanied by eGFR of ≤45 mL/min/1.73 m².

Worsening nephropathy was defined as doubling of the serum creatinine level and an eGFR of ≤45 mL/min/1.73 m², the need for continuous renal-replacement therapy, or death due to renal events in EMPA-REG OUTCOME; 40% reduction in eGFR, renal-replacement therapy, or death from renal causes in CANVAS; sustained decrease of ≥40% in eGFR to <60 mL/min/1.73 m², new end-stage renal disease, or death from any cause in DECLARE-TIMI 58; ESKD, doubling of the creatinine level, or renal death in CREDENCE.

§Pooled data from CANVAS and CANVAS-R.

CANVAS = CANagliflozin cardioVascular Assessment Study; CKD = chronic kidney disease; CREDENCE = Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; CV = cardiovascular; DAPA-HF = Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure; DECLARE-TIMI 58 = Dapagliflozin Effect on Cardiovascular Events . Thrombolysis in Myocardial Infarction 58; eGFR = estimated glomerular filtration rate; EMPA-REG = EMPAgliflozin cardiovascular outcome event trial in type 2 diabetes mellitus patients . Removing Excess Glucose; ESKD = end-stage kidney disease; HFrEF = heart failure with reduced ejection fraction; HHF = hospitalisation for heart failure; HR = hazard ratio; MI = myocardial infarction; NI = non-inferiority; PEP = primary end point; SGLT2 = sodium.glucose cotransporter-2; T2DM = type 2 diabetes mellitus; UA= unstable angina.