Range of adiposity and cardiorenal syndrome

Table 6 Major sodium-glucose cotransporter 2 inhibitors clinical trials and cardiorenal outcomes

Trial	n (follow-up)	BMI > 30	eGFR < 60 mL/min per 1.73 m2	CVD and HF	Diabetes	CVO and RO (HR; significant)
EMPA-REG[175] (empagliflozin vs PBO)	7020 (3.1 yr)	51%	25.9%	99.2% and 10.1%	About 100%	CVO1,2,3,4 RO6,7,8,9,10
CANVAS[172] (canagliflozin vs PBO)	10142 (2.4 yr)	59%	20,1%	65.6% and 14.4%	About 100%	CVO1,3 RO6,7,8,9
DECLARE-TIMI[174] (dapagliflozin vs PBO)	17160 (4.2 yr)	60%	7.4%	40.6% and 10%	About 100%	CVO1,3 RO6,7
CREDENCE[173] (canaglifozin vs PBO)	4401 (2.6 yr)	54.4%	60%	50.4% and 15%	52%	RO6,7,8,9 CVO1,2,3,4
DAPA-HF[176] (dapagliflozin vs PBO)	2373 (18.2 mo)	35%	26.1%	55.5% (IHD) and 100% (HFrEF)	41%	CVO1,2,3 RO: NS HFrEF: Better dapagliflozin
DAPA-CKD[194] (dapagliflozina vs PBO)	4304 (NA)	NA	About 90%	NA	Non-DM: ≥ 30%	Outcomes expected in 2020 (composite renal and secondary CV endpoints)
EMPEROR-Preserved[195] (empagliflozin vs PBO)	5988 (NA)	NA	NA (eGFR ≥ 20)	HFpEF (100%)	NA	Outcomes expected late in 2020 (composite CV, HF and secondary R endpoints)
EMPEROR-Reduced[196] (empaglifozin vs PBO)	3730 (NA)	NA	NA (eGFR ≥ 20)	HFrEF (100%)	NA	Outcomes expected late in 2020 (composite CV, HF and secondary RO)

¹Composite of worsening heart failure or cardiovascular death.

²Cardiovascular death.

³Heart failure hospitalization.

⁴Major adverse cardiovascular events (MACE) (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke). ⁵Extended MACE.

⁶Composite renal outcomes (doubling of serum creatinine, ≥ 40% (or 50%) decrease in estimated glomerular filtration rate (eGFR), new end-stage renal disease (ESRD), or death from renal or cardiovascular causes.

⁷New ESRD (chronic dialysis or renal transplant).

⁸Sustained reduction of ≥ 40% eGFR.

⁹Progression to macroalbuminuria.

¹⁰Doubling of serum creatinine levels. BMI: Body mass index; ACR: Albumin-to-creatinine ratio; CV: Cardiovascular; CVO: Cardiovascular outcomes; eGFR: Estimated glomerular filtration rate; ERSD: End-stage renal disease; HR: Hazard ratio; NA: Not available; PBO: Placebo; R: Renal; RO: Renal outcomes; NS: Not significant; O: Outcomes; HF: Heart failure; HFrEF: Heart failure with reduced ejection fraction; HFpEF: Heart failure with preserved ejection fraction; CVD: Coronary artery disease, peripheral arterial, myocardial infarction, ischemic stroke, endarterectomy carotid.