Metformin in renal failure--weigh the evidence

Sir, I am provoked to write this letter by your editorial comment [ 1 ] ‘…it is well known that metformin can cause lactic acidosis… . Thus, the use of metformin is considered to be contraindicated in subjects with CKD stages 3–5.’ The Cochrane review [ 2 ] states: ‘Pooled data from 206 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 47,846 patient-years of metformin use…’, and concludes: ‘There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments if prescribed under the study conditions.’ Analysis of the UK-based General Practice Research Database [ 3 ] revealed that ‘among the study population of 50,048 type 2 diabetic subjects, six cases of lactic acidosis during current use of oral antidiabetes drugs were identified, yielding a crude incidence rate of 3.3 cases per 100,000 person-years among metformin users and 4.8 cases per 100,000 person-years among users of sulfonylureas. Relevant comorbidities known as risk factors for lactic acidosis could be identified in all case subjects’. Metformin is the most effective of the oral antidiabetic agents, and has the merit of being the cheapest, as well as having the least propensity to induce hypoglycaemia. It is the most valuable antidiabetic drug in developing countries. Many physicians and nephrologists in poorer countries depend on metformin, and I personally [ 4,5 ] have extensive experience with its use, including in more than 1000 diabetics with CKD stages 3 and 4. I have never seen lactic acidosis due to metformin. A PubMed search reveals many reports of lactic acidosis in patients on metformin. On perusal, one finds that most of them had diseases that would cause lactic acidosis anyway, and just happened to be on metformin. Consider what might happen if we in the poor countries take your recommendation seriously. We have several times the number of diabetics that you would see in the developed world. We should prescribe insulin for all those who reach CKD stages 3 and 4. Apart from costing several times as much as metformin, insulin requires the patient to buy disposable sterile syringes. Most Indians cannot pay so much, and this would leave diabetes untreated if they are denied medicine they can afford. The physician should obviously be watchful and should withdraw metformin in patients who develop complications that might predispose to lactic acidosis, particularly fever and dehydration. I do not use it in CKD stage 5. For the rest, I respectfully disagree with your recommendations and will continue to use metformin as long as it is effective. Conflict of interest statement . None declared.