Table 2. Pharmacokinetic characteristics of SGLT2 inhibitors.

Drug	Metabolism (%)	Excretion unchanged (%)	Protein binding	Metabolic enzymes	Transporters	In vitro assessment of drug interaction	References
Dapagliflozin	75% of dose	< 2% and 15% of dose via urine and feces, respectively	91%	UGT1A9 (major)/CYP (minor)	Substrate of P-gp (dapagliflozin), OAT3 (metabolite)	Not inhibit: CYP 1A2, 2C9, 2C19, 2D6, or 3A4/P-gp, OCT2, OAT1, or OAT3; not induce: CYP1A2, 2B6, or 3A4	[58,59,60,61,62,63]
Empagliflozin	7.8–13.2% of dose in urine and 1.9% of dose in feces	75.5–77.4% of plasma radioactivity	86.2%	UGT2B7, UGT1A3, UGT1A8, UGT1A9	Substrate of P-gp, BCRP, OAT3, OATP1B1, OATPB3/not substrate of OAT1 and OCT2	Not inhibit: CYP isoforms/UGT1A1, UGT1A3, UGT1A8, UGT1A9, or UGT2B7/P-gp, BCRP, OAT3, OATP1B1, OATPB3; not induce: CYP isoforms	[67,68,70]
Ertugliflozin	< 45.9% of administered dose	35.3% of administered dose	Protein binding: 95%	UGT1A9 and UGT2B7, CYP (minor)	Substrate of P-gp, BCRP/not substrate of OAT1, OAT3, OCT1, OCT2, OATP1B1, OATP1B3	Weakly inhibit: UGT1A1, UGT1A4; not inhibit: CYP1A2, CYP2C9, CYP2C19, CYP2C8, CYP2B6, CYP2D6, CYP3A4/UGT1A6, UGT1A9, UGT2B7/P-gp, OCT2, OAT1, OAT3, OATP1B1, OATP1B3 (at clinically relevant concentration); not induce: CYP1A2, 2B6, or 3A4	[71,72,73]
Ipragliflozin	> 66.9% of administered dose	< 33.7% of administered dose	94.6–96.5%	UGT2B7 (major), UGT2B4, UGT1A9 (minor)	Substrate of P-gp	Not inhibit or weakly inhibit: CYP1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, 4A11/UGT1A1, 1A4, 1A6, 1A9, 2B7; not induce: CYP1A2, CYP3A4	[74,75,76]

UGT, UDP-glucuronosyltransferase; P-gp, P-glycoprotein; CYP, cytochrome P450; OCT, organic cation transporter; OAT, organic anion transporter; BCRP, breast cancer resistance protein.