FDA Permits Use of Metformin in Some Diabetes Patients With Mild to Moderate Kidney Failure

• FDA approves the use of metformin for some type II diabetes patients with mild-to- moderate renal disease.
• Metformin was earlier not recommended for use by FDA in these patients due to possible risk of lactic acidosis.
• Patients with mild-to-moderate kidney disease can now use metformin if their eGFR tests indicate levels within permissible limits.

The FDA has now approved the use of metformin for certain patients with mild-to-moderate kidney disease. This comes after decades of warning against the use of this drug in the treatment of renal disease patients due to the possible risk of lactic acidosis (lactic acid buildup in the bloodstream).

Metformin

Metformin has been in use over the past 20 years as a drug for patients with type II diabetes to control blood sugar levels. The UK Prospective Diabetes Study (UKPDS) has shown that the use of metformin in patients newly diagnosed with type II diabetes lowers cardiovascular morbidity and total mortality.

In the UKPDS, 342 newly diagnosed type II diabetes patients were treated with metformin and were compared with patients on conventional diet treatment. The study found that among patients undergoing metformin therapy, there was a:

• 39% reduction in risk for heart attack
• 36% reduction in risk for total mortality

The benefits of metformin therapy were evident even in an 8.5 year post trial monitoring. There were no similar benefits for patients who underwent sulfonylurea or insulin therapy.

Metformin is particularly useful for obese patients since it does not result in weight gain. Another benefit is that it does not cause hypoglycemia or low blood glucose levels. Hypoglycemia is a worrying factor for patients undergoing treatment for type II diabetes. This drug is also effective in preventing diabetes among people at high risk for developing type II diabetes.

Contra-indications for Metformin

Despite several positive effects associated with the use of metformin, its use is restricted due to the development of lactic acidosis among a small percentage of people with type II diabetes. An earlier drug related to metformin called phenformin increased the risk for lactic acidosis 10 to 20% more frequently than metformin. However, the negative experiences that were caused due to the use of phenformin led to the extra cautious use of metformin.

Since the elimination of metformin is largely by the kidneys, it was important to set a threshold for renal function while prescribing metformin. Patients were required to undergo a test for creatinine concentration and were prescribed metformin only when their creatinine levels were above the following levels:

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Men: 1.5 mg/dL

Women: 1.4 mg/dL

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The actual creatinine level till which metformin can be used is between 1.8 and 2.0 mg/dL. However, lower cut-off levels were recommended to ensure that the patient is not harmed in the event of inadequate check-ups or drug accumulation over time.

In a study conducted by Lalau JD and colleagues titled “Lactic Acidosis in Metformin-Treated Patients” and published in The International journal of Clinical Pharmacology and Therapeutics showed that metformin was efficiently cleared among patients with mild-to-moderate renal disease. In this study, 24 patients aged between 70-88 years were treated using metformin and it was found that:

• After a period of 2 months of using metformin, the level of the drug remained within therapeutic levels in the body. Lactate was also within reference limits.
• There was no statistical difference between the levels of metformin and lactate among patients with renal impairment and without.

Many similar studies have encouraged the FDA to re-consider its approval of the drug for control of type II diabetes to include patients even with mild to moderate kidney disease. The cutoff levels are now based on the estimated Glomerular Filtration Rate (eGFR), which is a diagnostic technique based on parameters like age, race and sex of the patient along with creatinine levels.

FDA Recommendations for Metformin Based on eGFR

• For patients with eGFR below 30 mL/minute per 1.73 m², metformin is contraindicated
• For patients with eGFR between 30 and 45 mL/minute per 1.73 m², the use of metformin is not recommended
• A minimum of annual eGFR testing should be done in patients on metformin
• Frequent testing should be done for elderly patients and others at risk for renal impairment

Studies have thus proved that metformin for type II diabetes may be used in certain patients with mild-to-moderate kidney impairment. This will make the use of this cheap and effective drug more widespread, aiding immensely in the care of patients with type II diabetes.

References:

1. http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm
2. Lipska KJ, Bailey CJ, Inzucchi SE. Use of Metformin in the Setting of Mild-to-Moderate Renal Insufficiency. Diabetes Care 2011;34 (6): 1431-1437
3. Herrington WG, Levy JB. Metformin: effective and safe in renal disease? Int Urol Nephrol. 2008;40(2):411-7.

Source-Medindia