Table 1.

Studies comparing risk renal outcomes among patients with CKD treated with SGLT2i.

Study	Population	Sample size	Intervention	Outcome	Results
EMPA-REG OUTCOME study (86)	T2DM at high risk for cardiovascular events	7,020 empagliflozin 10 mg (n = 2,345), 25 mg (n = 2,342), or matching placebo (n = 2,333)	empagliflozin 10 mg vs. empagliflozin 25 mg vs. placebo	Incident or worsening nephropathy (progression to macroalbuminuria, doubling of the serum creatinine level, initiation of renal-replacement therapy, or death from renal disease) and incident albuminuria.	Improvement of incident or worsening nephropathy (such as doubling of serum creatinine) for empagliflozin vs. placebo (12.7% vs. 18.8%, HR 0.61, 95% CI 0.53–0.70; p < 0.001), decrease of progression to macroalbuminuria (11.2 vs. 16.2%, p < 0.001)
CANVAS study (88)	T2DM at high risk for cardiovascular events	10,142 canagliflozin (n = 5,795) vs. placebo (n = 4,347	canagliflozin 100, 300 mg vs. Placebo	Progression of albuminuria	Canagliflozin was also associated with a lower rate of progression of albuminuria (p < 0.05)
DECLARE-TIMI 58 (91)	T2DM and established CV disease or risk factors for atherosclerotic CV disease	17,160 dapagliflozin 10 mg (n = 8,582) or placebo (n = 8,578).	dapagliflozin 10 mg vs. Placebo	≥40% decrease in eGFR to <60 mL/min/1.73 m2 or new end-stage renal disease or death from renal/CV cause	The incidence of the renal composite outcome was 4.3% in the dapagliflozin group and 5.6% in the placebo group (hazard ratio, 0.76; 95% CI, 0.67–0.87).
VERTIS CV study (115)	T2DM and established CV disease	8,246 ertugliflozin 5 mg (n = 2,752), 15 mg (n = 2,747), or placebo (n = 2,747)	Ertugliflozin 5, 15 mg vs. Placebo	Renal death or dialysis/transplant or doubling of serum creatinine from baseline	Renal composite (renal death, dialysis/transplant, doubling of serum creatinine) not achieve statistical significance (3.2 vs. 3.9%, p = 0.08.
CREDENCE study (92)	CKD and T2DM	4,401 canagliflozin 100 mg daily (n = 2,202) or placebo (n = 2,199)	canagliflozin Vs. Placebo	Composite of ESRD (dialysis, transplantation, or sustained estimated GFR of <15 mL/min/1.73 m2), doubling of the serum creatinine, or death from renal or cardiovascular causes.	ESRD, doubling of serum creatinine, renal or cardiovascular (CV) death, for canagliflozin vs. placebo, was 43.2 vs. 61.2 per 1,000 patient-years (P-Y) (p = 0.00001)
DELIGHT study (116)	T2DM and chronic kidney disease of moderate to severe grade	1,187 dapagliflozin group (n = 145), dapagliflozin–saxagliptin group (n = 155), placebo group (n = 148)	dapagliflozin 10 mg only, dapagliflozin 10 mg and saxagliptin 2.5 mg, or placebo once-daily	Worsening nephropathy and progression of albuminuria	Dapagliflozin with or without saxagliptin, in addition to ACE-i or ARBs, slows the progression of kidney disease in patients with diabetes and chronic insufficiency from moderate to severe.
CANTATA-SU (117)	T2DM patients already treated with metformin	1,450 Canagliflozin 100 mg (n = 483), Canagliflozin 300 mg (n = 485), Glimepiride (n = 482)	canagliflozin 100 mg or 300 mg/day vs. glimepiride 6–8 mg/day	Decrease in eGFR and progression of albuminuria.	It showed a reduction in eGFR: −0.5 (canagliflozin 100 mg), −0.9 (canagliflozin 300 mg), −3.3 (glimepiride) mL/min/1.73 m2 at 2 years; and a reduction of albuminuria: −31.7% (canagliflozin 100 mg), −49.3% (canagliflozin 300 mg) relative to glimepiride.
DERIVE study (118)	Type 2 diabetes and chronic kidney disease in stage IIIA	302 dapagliflozin 10 mg (n = 160) or placebo (n = 161)	dapagliflozin vs. placebo	This study assessed the efficacy and safety of dapagliflozin 10 mg vs. placebo in patients with T2DM and moderate renal impairment (estimated glomerular filtration rate [eGFR], 45–59 mL/min/1.73 m2; chronic kidney disease [CKD] stage 3A)	This study underlines the positive benefit and poor risk profile of dapagliflozin for the treatment of patients with T2D and CKD 3A.
DIAMOND study (119)	CKD in patients with non-diabetic kidney disease	58 dapagliflozin then placebo (n =27) and placebo then dapagliflozin (n =26)	dapagliflozin vs. Placebo	Change in 24-hr proteinuria and GFR in patients with non-diabetic kidney disease	This study showed that 6-week treatment with dapagliflozin did not affect proteinuria in this sample, but induced an acute and reversible reduction of eGFR.
DAPA-CKD study (85)	CKD in patients with non-diabetic kidney disease	4,304 dapagliflozin 10 mg (n = 2,152) placebo (n = 2,152)	Dapagliflozin vs. Placebo	Occurrence of one of the components of the composite: ≥50% sustained decline in eGFR or reaching End Stage Kidney Disease or CV death or renal death	The risk of a composite endpoint was significantly lower with dapagliflozin than with placebo, regardless of the presence or absence of T2DM.