etformin is first-line therapy for the management of type 2 diabetes mellitus, based on the American Diabetes Association and American College of Clinical Endocrinology guidelines.
Unless there is a contraindication, metformin should be considered part of a patient’s regimen for type 2 diabetes mellitus. A controversial contraindication for metformin is renal disease or dysfunction. Absolute cut-offs in serum creatinine has been published as times to discontinue metformin therapy (≥1.4 mg/dL for women; ≥1.5 mg/dL for men).
Lipska KL, et al, published recommendations for metformin among patients with mild to moderate renal dysfunction. This publication has been used in clinical practice to support “relaxed” dosing of metformin. Based on this publication in Diabetes Care (2011), the following recommendations were suggested:
- For patients with estimated glomerular filtration rate (eGFR) above 60, then metformin can be continued and renal function should be monitored on an annual basis.
- For patients with eGFR between 45 and 60, then metformin can be continued but the frequency of monitoring increases to every 3 or 6 months.
- For patients with eGFR between 30 and 45, there are several options depending on the individual. These options include lowering the dose by 50%; increasing the monitoring of renal function; or discontinuing metformin. For patients with a baseline eGFR 30 and 45, metformin should not be initiated.
- For patients with eGFR less than 30, then metformin should be stopped (if prescribed) or not initiated (if considered for new patients).
As diabetes educators, it is essential to check package inserts and/or drug references for the method (CrCl or eGFR) to assess renal function and appropriate dose adjustments.
On Friday, April 8, the Food and Drug Administration (FDA)
released a drug safety communication about metformin and reduced renal function. Based on published data, metformin can be used among certain individuals with declining renal function. The following recommendations are suggested:
- Before the initiation of metformin, obtain the patient’s estimated GFR (eGFR).
- For all patients on current metformin therapy, obtain an annual eGFR.
- Estimated GFR can be assessed more frequently among patients with risk factors for declining renal function (i.e. elderly patients).
- Do not use metformin among patients with an eGFR less than 30.
- Do not start metformin among patients with an eGFR between 30 to 45.
- Stop metformin if a patient’s eGFR drops less than at any point during therapy.
- Complete a risk-benefit analysis of metformin if a patient’s eGFR drops to less than 45.
- Stop metformin prior to iodinated contrast imaging procedure, especially among those patients with eGFR between 30 to 60. Re-evaluate renal function after 48 hours; if normal, metformin can be re-initiated.
In summary, the Modification of Diet in Renal Disease (MDRD) equation has been increasingly used to determine eGFR and evaluate renal function in clinical practice.
As diabetes educators, it is essential to check package inserts and/or drug references for the method (CrCl or eGFR) to assess renal function and appropriate dose adjustments. For example, canagliflozin (and other sodium glucose co-transporter 2 inhibitors) are based on eGFR for any dose adjustments.
In comparison, the doses of sitagliptin and alogliptin can be adjusted based on creatinine clearance (CrCl). Overall, there is evidence to support metformin among patients with mild renal impairment and certain individuals with moderate renal impairment.
Note: The units for eGFR are mL/min/1.73m2.
About the Author
Jennifer Clements received her Doctorate of Pharmacy from Campbell University in 2006 and completed a primary care residency at a Veterans Affairs Medical Center in 2007. She is also a certified diabetes educator and board certified in pharmacotherapy. Currently, she is the Interim Chair and Associate Professor in the Department of Pharmacy Practice at Presbyterian College School of Pharmacy.