Topic Discussion: Metformin and CKD

The package insert of Metformin says

“Renal disease or renal dysfunction (e.g., as suggested by serum creatinine levels 2 I .5 mg/dL [males], 2 1.4 mg/dL [females] or abnormal creatinine clearance) which may also result from conditions such as cardiovascular collapse (shock), acute myocardial infarction, and septicemia (see WARNINGS and PRECAUTIONS). “

This is dated back when this drug was introduced decades ago.  Most physicians withhold this very useful agent in most patients with a crt >1.4mg/dl.  But cautious use have been tried by many in advanced CKD and there are not many cases of lactic acidosis. 

This well done study in JAMA by Inzucchi et al reviewed over 800 publications on this topic of CKD and use of metformin from 1950 and 2014 and looked at major studies, case series and retrospective data.

What did they find?

1.       Lactate level was normal in patients with GFR of 60-90ml/min and even in patients with GFR of 30-60ml/min

2.       Most cases of lactic acidosis occurred in setting of a “second hit”- such as volume depletion, sepsis, AKI. Etc

3.       The rate of lactic acidosis in patients taking metformin was same as lactic acidosis in patients not taking metformin

4.       What did they recommend: 

Not to initiate metformin in patients with GFR< 45cc/min
Contraindicated in patients with GFR <30cc/min

5.       They recommended max doses based on GFR:

If GFR >60- max dose 2550mg per day

If GFR 45-59- max dose 2000mg per day

If GFR 30-44- max dose of 1000mg per day

Maybe it’s time we liberalize our guidelines to use metformin in CKD. Look what the Australians and Canadians are doing.