Table 2.
Antihyperglycemic agents dosing and considerations in advanced chronic kidney disease (labels reviewed as of April 1, 2020)
| Medication | Metabolism and excretion | Labeling dosing recommendations by GFR (mL/min/1.73 m2) | Dose in ESKD and/or dialysis |
|---|---|---|---|
| Biguanides | |||
| Metformin | Kidney | No dose adjustment if eGFR > 45 mL/min/1.73 m2 Do not start and reduce dose if already on therapy and eGFR 30 to 45 mL/min/1.73 m2 Discontinue if eGFR < 30 mL/min/1.73 m2 | Contraindicated because of risk of lactic acidosis |
| Second-generation sulfonylureas | |||
| Glipizide | Liver Excretion of < 10% of unchanged drug in urine | No dose adjustment if eGFR > 50 mL/min/1.73 m2 | No adjustment, but conservative initial dose (eg, 2.5 mg daily) recommended Use with caution long-acting formulations because of risk of hypoglycemia |
| Glimepiride | Liver Excretion in urine 60% of drug | Consider alternative if eGFR < 15 mL/min/1.73 m2 | Start lower dose of glimepiride (eg, 1 mg daily), caution recommended because of risk of hypoglycemia |
| Glyburide | Kidney Excretion of 50% of drug in urine | Avoid use | Contraindicated |
| Meglitinides | |||
| Nateglinide | Liver Excretion of 75% to 80% of drug in urine | No dose adjustment if eGFR > 30 mL/min/1.73 m2 | Initiate conservatively at 60 mg with meals if eGFR < 30 mL/min/1.73 m2 |
| Repaglinide | Liver Minimal excretion of parent drug in urine | No dose adjustment if eGFR > 30 mL/min/1.73 m2 | Initiate conservatively at 0.5 mg with meals if eGFR < 30 mL/min/1.73 m2 |
| DDPIV inhibitors | |||
| Sitagliptin | Kidney Excretion of 87% of unchanged drug in urine | 100 mg daily if eGFR > 50 mL/min/1.73 m2 50 mg daily if eGFR 30 to 50 mL/min/1.73 m2 25 mg daily if eGFR < 30 mL/min/1.73 m2 | Maximum dose of 25 mg daily |
| Saxagliptin | Liver/Kidney Excretion of 60% unchanged drug or active metabolite in urine | No dose adjustment if eGFR ≥ 45 mL/min/1.73 m2 Dose of 2.5 mg daily if eGFR ≤ 45 mL/min/1.73 m2 | Maximum dose of 2.5 mg daily |
| Linagliptin | Liver Excretion of < 5% to 7% of drug in urine | No dose adjustment | No dose adjustment |
| Alogliptin | Kidney Excretion of 60% to 71% of unchanged drug in urine | 25 mg daily if eGFR > 60 mL/min/1.73 m2 12.5 mg daily if eGFR 30 to 60 mL/min/1.73 m2 6.25 mg daily if eGFR < 30 mL/min/1.73 m2 | 6.25 mg daily |
| GLP1 RA agonists | |||
| Exenatide | Proteolytic degradation following glomerular filtration Excretion of majority of dose in the urine | No dose adjustment if eGFR > 50 mL/min/1.73 m2 Caution when initiating or escalating doses if eGFR 30 to 50 mL/min/1.73 m2 Not recommended with eGFR < 30 mL/min/1.73 m2 | Contraindicated |
| Lixisenatide | Proteolytic degradation and glomerular filtration | No dose adjustment required for eGFR 60 to 89 mL/min/1.73 m2 No dose adjustment required for eGFR 30 to 59 mL/min/1.73 m2, but monitor patients for side effects and changes in kidney function Clinical experience is limited with eGFR 15 to 29 mL/min/1.73m2; monitor patients for side effects and changes in kidney function | Avoid if eGFR < 15 mL/min/1.73 m2 |
| Albiglutide | Proteolytic degradation | No dose adjustment required for eGFR 15 to 89 mL/min/1.73 m2 Use caution with initiation or escalating doses and monitor for gastrointestinal reactions in patients with CKD | Not recommended |
| Liraglutide | Proteolytic degradation (not specific organ as a major route of elimination) Intact drug not detected in urine | No dose adjustment Post-marketing studies showed increased risk of gastrointestinal effects with higher doses Monitor for gastrointestinal reactions in patients with CKD | No dose adjustment Postmarketing studies showed increased risk of gastrointestinal effects with higher doses |
| Dulaglutide | Proteolytic catabolism | No dose adjustment | No dose adjustment Monitor eGFR in patients with CKD reporting severe adverse gastrointestinal reactions |
| Semaglutide injectable | Proteolytic cleavage of peptide backbone and sequential beta-oxidation of fatty acid sidechain Excretion of 3% of unchanged drug in urine | No dose adjustment Monitor eGFR function when initiating or escalating doses or in patients with adverse gastrointestinal reactions | No dose adjustment No clinically relevant change in semaglutide pharmacokinetics |
| Semaglutide oral | No dose adjustment Monitor eGFR when initiating or escalating doses or in patients with adverse gastrointestinal reactions | No dose adjustment No clinically relevant change in semaglutide pharmacokinetics | |
| SGLT2 inhibitors | Expected not to be effective for glycemic control in advanced CKD | ||
| Canagliflozin | Liver Excretion of < 1% of unchanged drug in urine | No dose adjustment if eGFR ≥ 60 mL/min/1.73 m2 100 mg daily if eGFR 45 to 59 mL/min/1.73 m2 Avoid use and discontinue in patients with eGFR persistently < 45 mL/min/1.73 m2 | Contraindicated |
| Dapagliflozin | Liver Excretion of < 2% of unchanged drug in urine | Avoid initiating if eGFR < 60 mL/min/1.73 m2 Not recommended with eGFR 30 to 60 mL/min/1.73 m2 | Contraindicated with eGFR < 30 mL/min/1.73 m2 Unknown effect of hemodialysis |
| Empagliflozin | Liver Excretion of25% to 50% of unchanged drug in urine | No dose adjustment required if eGFR ≥ 45 mL/min/1.73 m2 | Avoid use and discontinue in patients with eGFR persistently < 45 mL/min/1.73 m2 |
| Ertugliflozin | Liver Excretion of1% of unchanged drug in urine | No dosage adjustment or increased monitoring needed in patients with mild CKD Safety and efficacy in mild-to-moderate CKD not established | Contraindicated |
| Alpha glucosidase inhibitors | |||
| Acarbose | Intestinal | Avoid if eGFR < 30 mL/min/1.73 m2 | Contraindicated |
| Miglitol | Intestinal | Avoid if eGFR < 25 mL/min/1.73 m2 | Contraindicated |
| Thiazolidinediones | |||
| Pioglitazone | Liver Excretion of negligible amount of unchanged drug in urine | No dose adjustment | No dose adjustment recommended Caution with use given fluid retention and adverse effects on bone metabolism |
| Amylin analog | |||
| Pramlintide | Kidney | No dose adjustments for eGFR > 20 to <50 mL/min/1.73 m2 | No studies performed |
Abbreviations: CKD, chronic kidney disease; DDPIV, dipeptidyl peptidase-4; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; GLP1 RA, glucagon-like peptide receptor-1; SGLT2, sodium-glucose loop transporter-2.