Is it safe to increase metformin (biguanide) to 1gm twice daily (bid) in a patient with moderate impaired renal function (GFR of 54)?

From the Guidelines

Increasing metformin to 1 gram twice daily is not recommended for a patient with a GFR of 54 mL/min/1.73m², as the maximum recommended dose should be limited to 1000 mg per day total to minimize the risk of lactic acidosis. According to the most recent guidelines, metformin may be safely used in people with estimated glomerular filtration rate ≥30 mL/min/1.73 m² 1. However, for patients with a GFR between 45-59 mL/min/1.73m², dose reduction is necessary to maintain safety. The patient's renal function should be monitored regularly, at least 2-4 times per year, and metformin should be immediately discontinued if GFR drops below 30 mL/min/1.73m² or if the patient experiences conditions that may worsen renal function (severe infection, dehydration, contrast dye exposure) 1. Alternative diabetes medications with less dependence on renal clearance might be considered if better glycemic control is needed.

Some key points to consider:

• Metformin is primarily eliminated by the kidneys, and reduced renal function leads to drug accumulation, increasing the risk of lactic acidosis—a rare but serious side effect 1.
• The risk of lactic acidosis is very low in absolute terms, but it is still a concern in patients with reduced renal function 1.
• Regular monitoring of renal function and adjustment of the metformin dose as needed is crucial to minimize the risk of lactic acidosis 1.
• Alternative diabetes medications, such as SGLT2 inhibitors or GLP-1 receptor agonists, may be considered if better glycemic control is needed and metformin is not tolerated or contraindicated 1.

From the FDA Drug Label

2.3 Recommendations for Use in Renal Impairment

Assess renal function prior to initiation of metformin hydrochloride tablets and periodically thereafter. Metformin hydrochloride tablets are contraindicated in patients with an estimated glomerular filtration rate (eGFR) below 30 mL/minute/1.73 m 2. Initiation of metformin hydrochloride tablets in patients with an eGFR between 30 to 45 mL/minute/1. 73 m 2is not recommended. In patients taking metformin hydrochloride tablets whose eGFR later falls below 45 mL/min/1.73 m 2, assess the benefit risk of continuing therapy.

The patient's GFR is 54, which is above the threshold of 45 mL/min/1.73 m^2 where the benefit and risk of continuing therapy should be assessed. Key considerations:

• The patient's renal function is moderately impaired but not severely impaired.
• The recommended dose increase should be based on glycemic control and tolerability.
• The maximum dose of 2550 mg per day can be given in divided doses. It is possible to increase metformin to 1gm twice daily (bid) in a patient with a GFR of 54, but the decision should be made with caution and careful monitoring of renal function and glycemic control 2.

From the Research

Metformin Dosage and Renal Function

• The safety of increasing metformin to 1gm twice daily (bid) in a patient with a glomerular filtration rate (GFR) of 54 is a concern due to the potential risk of lactic acidosis 3, 4.
• However, some studies suggest that metformin can be used safely in patients with moderate renal impairment, including those with a GFR between 30-60 ml/min, as long as the dose is adjusted and caution is exercised 5, 6.
• A study published in 2018 recommends using metformin down to a GFR of 30 mL/min with adjusted doses, and stopping metformin only when GFR is below 45 mL/min in connection with administration of iodine contrast media 7.

Considerations for Dose Adjustment

• The daily dose of metformin should be reduced according to GFR or even contraindicated in presence of severe chronic kidney disease (CKD) due to the risk of lactic acidosis 3.
• Estimated GFR measurements can be used to guide metformin prescribing, with proposed pragmatic eGFR limits to guide metformin prescribing in patients with renal impairment 4.
• Determination of metformin levels in serum can be useful to guide therapeutic dose when GFR is low and to confirm that lactic acidosis is caused by metformin 7.

Clinical Decision-Making

• Physicians should weigh the evidence carefully before deciding to adjust or withdraw metformin therapy in patients with stable chronic kidney disease, considering the benefits and risks of metformin and alternative hypoglycaemic agents 5, 6.
• The risks and benefits of alternative hypoglycaemic agents should be considered carefully, taking into account the potential risks of severe hypoglycaemia and fluid retention associated with other treatments 6.