From the Guidelines
When stopping metformin due to chronic kidney disease (CKD), sodium-glucose cotransporter-2 (SGLT2) inhibitors like empagliflozin (Jardiance), dapagliflozin (Farxiga), or canagliflozin (Invokana) are generally the best alternative oral medications for most patients, as they provide kidney protection and reduce cardiovascular risk, making them particularly beneficial for patients with CKD 1. The choice of oral diabetic medication after discontinuing metformin due to CKD should prioritize medications that not only control blood glucose but also offer additional benefits such as kidney protection and reduction of cardiovascular risk.
Key Considerations
- SGLT2 inhibitors are recommended for patients with type 2 diabetes and CKD with an estimated glomerular filtration rate (eGFR) ≥20 ml/min/1.73 m², as they have proven kidney and cardiovascular benefits 1.
- For patients with more advanced kidney disease, glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors like sitagliptin (adjusted for kidney function) are good alternatives, as they enhance insulin secretion in response to meals and have minimal risk of hypoglycemia 1.
- The choice should be individualized based on the patient's specific CKD stage, cardiovascular risk factors, hypoglycemia risk, cost considerations, and other comorbidities.
Medication Options
- SGLT2 inhibitors:
- Empagliflozin (Jardiance) - typical starting dose is 10mg daily
- Dapagliflozin (Farxiga) - typical starting dose is 10mg daily
- Canagliflozin (Invokana) - typical starting dose is 100mg daily
- GLP-1 receptor agonists:
- Many are injectable rather than oral
- DPP-4 inhibitors:
- Sitagliptin - adjusted for kidney function
Important Considerations
- SGLT2 inhibitors should be used cautiously in patients with severe renal impairment (eGFR <30 ml/min/1.73m²) 1.
- Metformin may be continued in patients with CKD and eGFR ≥30 ml/min/1.73 m², with dose reduction as necessary 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Alternatives to Metformin in CKD
When discontinuing metformin due to Chronic Kidney Disease (CKD), the choice of oral diabetic medication depends on various factors, including the stage of CKD and the patient's overall health. Some alternatives to metformin include:
- DPP-4 inhibitors, which have been shown to be effective and safe in patients with CKD, including those on dialysis 2
- Other oral antidiabetic agents, such as sulphonylureas and thiazolidinediones, although these may have a higher risk of hypoglycemia and fluid retention, respectively
Considerations for Discontinuing Metformin
The decision to discontinue metformin in patients with CKD should be based on the individual patient's risk of lactic acidosis and the potential benefits of continued metformin therapy. Some studies suggest that metformin can be safely used in patients with mild to moderate CKD, with adjusted dosages and close monitoring 3, 4, 5, 6
- The risk of lactic acidosis is rare and may be overstated, with some studies suggesting that the benefits of metformin outweigh the risks in patients with CKD 5, 6
- However, the risk of lactic acidosis may be increased in patients with severe CKD, and metformin should be discontinued if renal function falls below a certain level or during acute renal deterioration 3
DPP-4 Inhibitors as an Alternative
DPP-4 inhibitors have been shown to be a safe and effective alternative to metformin in patients with CKD, with a low risk of hypoglycemia and no significant effect on kidney function 2
- These inhibitors can be used in patients with CKD, including those on dialysis, and have been shown to provide effective glycemic control without severe hypoglycemia or weight gain
- Additionally, DPP-4 inhibitors may have a kidney-protective effect, although further studies are needed to confirm this 2