Table 2.

Main clinical trials evaluating renal outcomes among patients treated with SGLT2-Is.

Drug	Trial (Ref.)	Patients	Follow-Up (Median)	Outcomes	Hazard Ratio (95% CI)
Empagliflozin	EMPAREG OUTCOME study [47]	7020 T2DM patients with high risk for CV events and eGFR ≥ 30 mL/min/1.73 m2	3.1 years (2.6 years of treatment)	incident or worsening nephropathy	0.61 (0.53–0.70)
				progression to macroalbuminuria	0.65 (0.54–0.72)
		empagliflozin 10 mg vs.		doubling of the serum creatinine level	0.56 (0.39–0.79)
		empagliflozin 25 mg vs.   placebo		initiation of renal-replacement therapy	0.45 (0.21–0.97)
				post hoc composite of doubling of serum creatinine, renal replacement therapy, or death for renal causes	0.54 (0.40–0.75)
				incident albuminuria	0.95 (0.87–1.04)
Canagliflozin	CANVAS–R study [46]	5812 T2DM patients with high risk for CV events and eGFR > 30 mL/min/1.73 m2	126.1 weeks	lower progression of albuminuria	0.73 (0.67–0.79)
		canagliflozin 100 or 300 mg vs. placebo		composite of 40% reduction in eGFR, renal replacement therapy, or death from renal causes	0.60 (0.47–0.77)
	CREDENCE study [105]	4401 T2DM patients with albuminuric CKD (eGFR of 30 to < 90 mL/min/1.73 m2)	2.62 years	composite of ESRD (dialysis, transplantation, or sustained eGFR < 15 mL/min/1.73 m2), doubling of serum creatinine, or death from renal or CV causes	0.70 (0.59–0.82)
		canagliflozin 100 mg vs. placebo		composite of ESRD, a doubling of the creatinine level, or death from renal causes	0.66 (0.53–0.81)
				composite of cardiovascular death, myocardial infarction, or stroke	0.80 (0.67–0.95)
				hospitalization for heart failure	0.61 (0.47–0.80)
Dapagliflozin	DECLARE-TIMI 58 [48]	7160 T2DM patients at high risk for CV events (only 7% with eGFR < 60 mL/min/1.73 m2)   dapagliflozin 10 mg vs. placebo	4.2 years	composite of ≥40% reduction in eGFR, new ESRD, or death from renal or CV causes	0.76 (0.67–0.87)
	DAPA-CKD study [106]	4304 diabetic (68%) or not diabetic patients suffering from CKD (UACR 200–5000 mg/g and eGFR 25–75 mL/min/1.73 m2)	2.4 years	composite of ≥50% sustained decline in eGFR or ESRD or CV or renal death	0.56 (0.45–0.69)
		dapagliflozin 10 mg vs. placebo		composite of CV death and hospitalization for heart failure	0.71 (0.55–0.92)
	DELIGHT study [107]	461 T2DM patients with albuminuria (UACR 30–3500 mg/g) and eGFR of 25–75 mL/min/1.73 m2, treated with ACE-Is or ARBs	24 weeks	variation of albumin-to-creatinine ratio	−21.0% for dapagliflozin (p = 0.011)
		dapagliflozin 10 mg vs.  dapagliflozin 10 mg–saxagliptin 2.5 mg vs.  placebo			−38.0% for dapagliflozin + saxagliptin (<0.0001)
	DERIVE study [108]	321 T2DM patients with CKD in stage 3A (eGFR of 45–59 mL/min/1.73 m2)  dapagliflozin 10 mg vs. placebo	24 weeks	change from baseline in urine eGFR	decrease at week 4 with a trend to recovery at weeks 12 and 24 eGFR similar to placebo after a 3 week period without treatment
	DIAMOND study [109]	53 non-diabetic patients with CKD (24-h urinary protein excretion > 500 mg and ≤3500 mg, eGFR ≥ 25 mL/min/1.73 m2) on stable RAS blockade   27 received dapagliflozin 10 mg then placebo   26 received placebo then dapagliflozin 10 mg	cross-over trial (6 weeks for each treatment and washout period)	mean proteinuria measured GFR	no significant change from baseline  change with dapagliflozin at week 6 by −6.6 mL/min/1.73 m2  (−9.0 to −4.2; p < 0.0001) (fully reversible within 6 weeks after dapagliflozin discontinuation)
Ertugliflozin	VERTIS CV study [92]	8246 T2DM patients with established CV disease and eGFR ≥ 30 mL/min/1.73 m2  ertugliflozin 5 or 15 mg vs. placebo	3 years	composite of death from renal causes, renal replacement therapy, or doubling of serum creatinine	0.81 (0.63–1.04)