. 2019 Feb 1;20(3):629. doi: 10.3390/ijms20030629

Table 2.

Relationship between SGLT2 inhibitor-induced changes in urine volume and urinary sodium excretion and RAS parameters.

	Subjects	Observation Period	RAS Parameters	Urinary Sodium Excretion	Urine Volume	SGLT2 Inhibitor	Reference
Animal Experiments	db/db mice	10 weeks	PRA increased by ~1.5 fold	N/A	Increased by ~1.06 fold	empagliflozin	[46]
	5/6 Nx SD rats	10 weeks	No change	N/A	N/A	luseogliflozin	[69]
	OLETF rats	12 weeks	PRA no change	N/A	N/A	dapagliflozin	[74]
			Urinary Ang II decreased by ~30 fold
			Urinary AGT decreased by ~5 fold
			Plasma aldosterone no change
Clinical Studies	Type 2 diabetes	Day 1	PRA no change	Increased by ~1.33 fold	Increased by ~3.71 fold	canagliflozin	[16]
		Day 1	Plasma aldosterone no change	Increased by ~1.33 fold	Increased by ~3.71 fold
		Day 5	PRA increased by ~2 fold	No change	Increased by ~1.03 fold
		Day 5	Plasma aldosterone no change	No change	Increased by ~1.03 fold
	Type 1 diabetes with hyperfiltration	8 weeks	PRA increased by ~1.11 fold, but this change was not significant	Increased by ~1.10 fold	Increased by ~1.56 fold	empagliflozin	[50]
			Plasma Ang II increased by ~1.56 fold
			Plasma aldosterone increased by ~1.72 fold
	Type 2 diabetes	4 days	PRA increased by ~1.0 fold, but this change was not significant	Increased by ~1.28 fold	Increased by ~1.6 fold	ipragliflozin	[53]
			Plasma Ang II no change
			Plasma aldosterone no change
	Type 2 diabetes	1 month	total urinary AGT/creatinine ratio no changed	N/A	N/A	canagliflozin, ipragliflozin, dapagliflozin, tofogliflozin, luseogliflozin	[75]
	Type 2 diabetes	1 month	PRA increased by ~3.0 fold	N/A	N/A	tofogliflozin, empagliflozin, canagliflozin	[76]
		1 month	Plasma aldosterone no change
		6 months	PRA no change
		6 months	Plasma aldosterone no change
	Type 2 diabetes	24 weeks	PRA increased by ~1.59 fold, but this change was not significant	N/A	N/A	Ipragliflozin	[77]
	Type 2 diabetes	24 weeks	Plasma aldosterone increased by ~1.27 fold	N/A	N/A	Ipragliflozin	[77]

SGLT2, sodium glucose cotransporter 2; RAS, renin angiotensin system; PRA, plasma renin activity; Nx, nephrectomy; SD, sprague dawley; OLETF, otsuka long-evans tokushima fatty; Ang II, angiotensin II; AGT, angiotensinogen.