Table 4.

Recommended dosing adjustments of antidiabetic drugs in patients with diabetes and CKD.

Class and Agents	References	Therapeutic Considerations
Biguanides	[65,66,67,68,69,71,72,73]
Metformin		Review use/reduce dose if eGFR < 45–60 mL/min/1.73 m2 Avoid if eGFR < 30 mL/min/1.73 m2 FDA is more restrictive indicating that metformin is contraindicated if serum creatinine ≥1.5 mg/dL (133 μmol/L) in males or ≥1.4 mg/dL (124 μmol/L) in females
Sulfonylureas	[65,69,70,74]
Glyburide (glibenclamide)		Not recommended if eGFR <60 mL/min/1.73 m2
Gliclazide		Reduce dose if eGFR <30 mL/min/1.73 m2 Not recommended if eGFR <15 mL/min/1.73 m2
Glimepiride		Reduce dose if eGFR <30 mL/min/1.73 m2 Start at 1 mg daily or consider alternative agent if eGFR < 15 mL/min/1.73 m2
Glipizide		Can be used in all stages of CKD with caution. May need dose reduction
Meglitinides	[65,70,75,76]
Repaglinide and Nateglinide		Can be used in all stages of CKD with caution. May need dose reduction if eGFR <30 mL/min/1.73 m2
DPP-4 inhibitors	[65,69,70]
Sitagliptin		Reduce dose to 50 mg daily if eGFR 30–50 mL/min/1.73 m2 and to 25 mg daily if eGFR <30 mL/min/1.73 m2
Saxagliptin		Reduce dose to 2.5 mg daily if eGFR <50 mL/min/1.73 m2 Administer postdialysis in hemodialysis requiring patients
Linagliptin		No restrictions
Vildagliptin		Reduce dose to 50 mg daily when eGFR <50 mL/min/1.73 m2
Thiazolidinediones	[65,69,70]
Rosiglitazone and Pioglitazone		No dose adjustment required
α-glucosidase inhibitors	[65,70,74,77,78]
Acarbose and Miglitol		Not recommended if eGFR <25 mL/min/1.73 m2 or serum creatinine >2 mg/dL
Voglibose		Not well studied but is minimally absorbed and dose reduction unlikely needed
GLP-1 analogs	[70,71,79,80,81,82,83,84,85,86]
Exenatide		Not recommended if eGFR <30 mL/min/1.73 m2
Liraglutide		Not recommended if eGFR <50 mL/min/1.73 m2
Albiglutide and Dulaglutide		Experience is limited. No dose adjustment required per FDA approval but the European Medicines Agency recommended avoiding their use in patients with GFR <30 mL/min/1.73 m2)
SGLT2 inhibitors	[72,87,88,89,90]
Dapagliflozin		Not recommended if eGFR <60 mL/min/1.73 m2
Canagliflozin		Reduce dose to 100 mg once daily if eGFR 45–60 mL/min/1.73 m2 Not recommended if eGFR <45 mL/min/1.73 m2
Empagliflozin		Reduced dose to 10 mg once daily if eGFR 45–60 mL/min/1.73 m2 Not recommended if eGFR <45 mL/min/1.73 m2
Insulin	[42,52,70]
Insulin		Use with caution. Dose reduction usually necessary if eGFR <30 mL/min/1.73 m2

GLP-1 = Glucagon-like peptide-1; DPP-4 = Dipeptidyl peptidase 4; SGLT2 = Sodium-glucose co-transporter 2.