Table 11.

Drugs for treatment of diabetes: Categorization according to their risk of DDIs and QTc prolongation when used concomitantly with ribociclib and palbociclib.

Antidiabetics	CYP3A4 Substrate	CYP3A4 Inhibitor	CYP3A4 Inducer	Membrane transporter substrate	TdP risk	Comments
Sulfonylureas: Glicazide Glibenclamide Glisentide Glipizide Gliquidone	– – – – –	– – – – –	– – – – –	OATP1B1 OATP1B3 – OATP1B3 –	Not known Not known Not known Not known Not known	Low risk of interaction with palbociclib and ribociclib SAFE OPTIONS
Alfa glycosidase inhibitors: Ascarbose Miglitol	– –	– –		– –	Not known Not known
GLP-1: Albiglutide Dulaglutide Exenatide Liraglutide lixisenatide	– – – – –	– – – – –	– – – – –	– – – – –	Not known Not known Not known Not known Not known
DPP-4 inhibitor: Vildagliptin Alogliptin Sitagliptin	– Minor –	– – –	– – –	– – gp-P	Not known Not known Not known
SGLT2 inhibitor: Canagliflozin Dapagliflozin	Minor –	– –	– –	gp-P gp-P	Not known Not known
Biguanides: Metformin	–	–	–	OCT2, OCT1, MATE 1/2	Not known	Caution should be exercised in combination with ribociclib or palbociclib
Meglitinides: Repaglinide	Major	–	–	OATP1B1/1B3	Not known	High risk of DDIs. Should be avoided the combination with ribociclib or palbociclib
DPP-4 inhibitor: Saxagliptin Linagliptin	Major Major	– –	– –	gp-P gp-P	Not known Not known

Green: Low risk of interaction with palbociclib and ribociclib, SAFE OPTIONS. Orange: Caution should be exercised. Red: High risk of DDIs. Plasmatic concentrations of the CYP3A4 substrate could be increased (or decreased) when used concomitantly with a CYP3A4 inhibitor (or inducer) moderate or strong. GLP-1: Glucagonlike-peptide 1; SGLT2: Sodium -glucosecotransporter 2; DPP-4: dipeptidylpeptidase IV; TdP,Torsades de pointes; gp-P, P-glycoprotein; OATP1B1, organic anion transporter polypeptide; OCT2, OCT1 organic cation transporter 1 and 2; MATE 1/2, multidrug and toxin extrusion 1 and 2