Table 1.

SGLT2 inhibitor-induced changes in urine volume and urinary sodium excretion.

	Subjects	Observation Period	Food Restriction, etc.	Urinary Sodium Excretion	Urine Volume	SGLT2 Inhibitor	Reference
Animal Experiments	ZDF rats	24 h	No	N/A	Increased by ~1.82 fold	dapagliflozin	[39]
	SD rats				Increased by ~5.0 fold
	Dogs	24 h	No	Increased by ~1.50 fold	Increased by ~3.7 fold	bexagliflozin or EGT1442	[40]
	ZDF rats	24 h	No	Increased by ~1.80 fold	Increased by ~1.82 fold	luseogliflozin	[41]
	db/db mice	4 weeks	No	N/A	Increased by ~1.27 fold	tofogliflozin	[42]
		8 weeks			No change
	Streptozotocin-nicotinamide induced type 2 diabetic mice	24 h	High fat diet	N/A	Increased by ~4.6 fold	ipragliflozin	[43]
	db/db mice	Day 1	No	Increased by ~1.40 fold	Increased by ~1.67 fold	empagliflozin	[44]
		7 days		No change	Increased by ~1.33 fold
	Streptozotocin induced type 1 diabetic rats	70 min	No	Increased by ~4.0 fold	Increased by ~2.28 fold	phlorizin	[45]
	SHRcp rats	5 weeks	No	Increased by ~1.30 fold	Increased by ~4.0 fold	luseogliflozin	[20]
	OLETF rats	12 h	0.5% NaCl diet	Increased by ~1.30 fold	N/A	empagliflozin	[23]
		5 weeks		N/A
	db/db mice	10 weeks	No	N/A	Increased by ~1.06 fold	empagliflozin	[46]
	Streptozotocin induced type 1 diabetic mice	3 weeks	No	N/A	Increased by ~1.17 fold	ipragliflozin	[47]
	C57BL/6J mice	16 weeks	High fat diet	N/A	Increased by ~4.0 fold	empagliflozin	[48]
	SD rats	120 min	No	Increased by ~7.0 fold	Increased by ~1.90 fold	luseogliflozin	[21]
Clinical Studies	Type 2 diabetes	12 weeks	Standard diet	No change	Increased by ~.26 fold	dapagliflozin	[38]
	Type 2 diabetes	12 weeks	Standard diet	N/A	Increased by ~1.25 fold	dapagliflozin	[49]
	Type 1 diabetes with hyperfiltration	8 weeks	High sodium (>140 mmol/d) and moderate protein (<1.5 g/kg/d) diet for 14 days	Increased by ~1.10 fold	Increased by ~1.56 fold	empagliflozin	[50]
	Type 2 diabetes	12 weeks	Sodium restricted diet (∼200 mmol/day)	Increased by ~1.22 fold	Increased by ~1.49 fold	canagliflozin	[18]
	Type 2 diabetes	Day 1	Isocaloric diet	N/A	Increased by ~1.14 fold	canagliflozin	[51]
		2 weeks			No change
	Type 2 diabetes	7 days	Standardized meal of approximately 600 kcal	N/A	Increased by ~1.19 fold	luseogliflozin	[52]
	Type 2 diabetes	4 days	No	Increased by ~1.28 fold	Increased by ~1.6 fold	ipragliflozin	[53]
	Type 2 diabetes	24 h	Standard diet	No change	Increased by ~1.27 fold	canagliflozin	[19]
		18 days			No change
	Type 2 diabetes	Day 1	No	Increased by ~1.33 fold	Increased by ~3.71 fold	canagliflozin	[16]
		Day 5		No change	Increased by ~1.03 fold
	Type 2 diabetes	6 months	Standard diet	Increased by ~1.40 fold	Increased by ~1.86 fold	ipragliflozin, dapagliflozin, tofogliflozin, luseogliflozin	[54]

SGLT2, sodium glucose cotransporter 2; ZDF, zucker diabetic fatty; SD, sprague dawley; SHRcp, metabolic syndrome SHR/NDmcr-cp (+/+); OLETF, otsuka long-evans tokushima fatty; N/A, not available.