- 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
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).
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.
‘Extending the use of metformin to patients with type II diabetes with mild-to-moderate kidney disease will aid in effective control of blood glucose levels in these patients.’
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:
reduction in risk for heart attack
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.
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.
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.
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:
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.
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:
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.
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
- Frequent testing should be done for elderly patients and
others at risk for renal impairment
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.
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
Herrington WG, Levy JB. Metformin: effective and
safe in renal disease? Int Urol Nephrol. 2008;40(2):411-7.