Table 2.

Recommended dosing of additional noninsulin glucose-lowering agents by eGFR^13,74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88

Medication	Labeled dosing recommendations by eGFR (ml/min/1.73 m2)
SGLT2 inhibitors
Canagliflozin	•eGFR ≥60: 100 mg once daily; may increase to 300 mg once daily for additional glycemic control
	•eGFR 30 to <60: 100 mg once daily
	•eGFR <30: initiation not recommended, however patients with albuminuria >300 mg/day may continue 100 mg once daily to reduce the risk of ESKD, doubling of serum creatinine, CV death, and hospitalization for HF
	•Dialysis: contraindicated
Dapagliflozin	•eGFR ≥45: Recommended starting dose of 5 mg once daily to improve glycemic control; 10 mg once daily for all other indications
	•eGFR 25 to <45: 10 mg once daily
	•eGFR <25: Initiation not recommended; may continue 10 mg once daily to reduce the risk of eGFR decline, ESKD, CV death, and hospitalization for HF
	•Dialysis: contraindicated
Empagliflozin	•eGFR ≥30: No dose adjustment required
	•eGFR <30: Use not recommended solely for improvement of glycemic control
	•Data are insufficient to provide dosing recommendations in patients: o With T2D and established cardiovascular disease with eGFR <30 ml/min/1.73 m2 o With HF and eGFR <20 ml/min/1.73 m2
	•Dialysis: contraindicated
Ertugliflozin	•eGFR ≥45: No dose adjustment required
	•eGFR <45: Use not recommended
	•Dialysis: contraindicated
GLP-1 receptor agonists
Dulaglutide	•No dose adjustment required
	•Use with caution in ESKD; monitor kidney function in patients reporting severe GI adverse events
Exenatide	Twice-daily Product:
	•CrCl 50–80 ml/min: no dose adjustment required
	•CrCl 30–50 ml/min: caution when initiating or increasing the dose
	•CrCl <30 ml/min: use not recommended
	Once-weekly product:
	•eGFR ≥45: no dose adjustment required
	•eGFR <45: use not recommended
Liraglutide	•No dose adjustment required
	•Use with caution in ESKD; exercise caution in patients experiencing dehydration
Lixisenatide	•eGFR >60: no dose adjustment required
	•eGFR 30 to <60: no dose adjustment recommended, but monitoring of kidney function and for GI reactions is recommended
	•eGFR 15 to <30: monitoring of kidney function and for GI reactions is recommended
	•eGFR <15: use not recommended
Semaglutide	No dose adjustment required
DPP-4 inhibitors
Alogliptin	•CrCl ≥60 ml/min: no dose adjustment required
	•CrCl 30 to <60 ml/min: 12.5 mg once daily
	•CrCl <30 ml/min: 6.25 mg once daily
Linagliptin	No dose adjustment required
Saxagliptin	•eGFR ≥45: no dose adjustment required
	•eGFR <45: 2.5 mg once daily
Sitagliptin	•eGFR ≥45: no dose adjustment required
	•eGFR 30 to <45: 50 mg once daily
	•eGFR <30: 25 mg once daily
Sulfonylureas (Second generation)
Glimepiride	•No specific dosing based on eGFR
	•Start conservatively at 1 mg and titrate slowly in CKD
Glipizide	•No specific dosing based on eGFR
	•Start conservatively (e.g., 2.5 mg once daily) and titrated slowly in CKD
Glyburide	Use not recommended
Thiazolidinediones
Pioglitazone	No dose adjustment required
Alpha-glucosidase inhibitors
Acarbose	eGFR <30: use not recommended
Miglitol	eGFR <25: use not recommended

CKD, chronic kidney disease; CrCl, creatinine clearance; CV, cardiovascular; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; GI, gastrointestinal; HF, heart failure; SGLT2, sodium glucose cotransporter-2; T2D, type 2 diabetes.