Metformin is the first-line oral antidiabetic drug for most patients with type 2 diabetes mellitus.Its advantages are good glycemic control; it also does not cause hypoglycaemia weight gain. Metformin is eliminated by the kidneys; hence, its use in chronic kidney disease has been restricted. Lactic acidosis has been reported with the use of metformin, which occurs when metformin accumulates in conditions of acute or progressive renal failure, acute or progressive heart failure, acute pulmonary decompensation, sepsis, dehydration. A rare side effect, but has a high case fatality rate.

Metformin was earlier indicated for use in patients with kidney disease with eGFR >60 mL/min/1.73 m2. It was contraindicated when serum creatinine level was > 1.4 mg/dL in woman and 1.5 mg/dL in men, and eGFR < 60 mL/min.

Then in 2012, the Kidney Disease Outcomes Quality Initiative(K/DOQI)guidelines recommended that metformin may be used among patients with an eGFR >45mL/min/1.73 m2. And, it is to be avoided in patients in whom the eGFR is <30mL/min/1.73 m2because of an increased risk of lactic acidosis.

In 2016, in what can be termed as a practice changing update, the US FDA revised its labelling of metformin to indicate that it may now be safely used in patients with mild to moderate renal impairment (30 to 60 mL/min/1.73 m2) but not in patients with severe renal impairment (<30 mL/min/1.73 m2).The labelling changes include:

1. Obtain eGFR before initiating treatment with metformin.
2. Use of metformin in patients with an eGFR below 30 mL/minute/1.73 m2is an absolute contraindication.
3. Starting metformin in patients with an eGFR between 30-45 mL/minute/1.73 m2is not recommended.
4. Prescribe full dose in patients with eGFR ≥45mL/min.
5. In patients with no active kidney disease and an eGFR of 30 to 44mL/min, reduce metformin dose by half.Monitor kidney function frequently.
6. eGFR should be obtained at least annually in all patients on metformin. In patients at increased risk for the development of renal impairment such as the elderly, renal function should be assessed more frequently.
7. In patients taking metformin whose eGFR later falls below 45 mL/minute/1.73 m2, assess the benefits and risks of continuing treatment.If the eGFR later falls below 30 mL/minute/1.73 m2, then discontinue metformin.
8. Discontinue metformin at the time of / prior to an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/minute/1.73 m2; in patients with a history of liver disease, alcoholism, or heart failure; or in patients who will be administered intra-arterial iodinated contrast. Re-evaluate eGFR 48 hours after the imaging procedure; restart metformin if renal function is stable.

(Source: Uptodate, US FDA)

Dr KK Aggarwal

Padma Shri Awardee

Vice President CMAAO

Group Editor-in-Chief IJCP Publications

President Heart Care Foundation of India

Immediate Past National President IMA