{"id":544,"date":"2015-01-23T11:00:02","date_gmt":"2015-01-23T11:00:02","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=544"},"modified":"2017-08-21T12:00:48","modified_gmt":"2017-08-21T12:00:48","slug":"primary-care-corner-with-geoffrey-modest-md-metformin-in-renal-failure","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/01\/23\/primary-care-corner-with-geoffrey-modest-md-metformin-in-renal-failure\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Metformin in renal failure"},"content":{"rendered":"

By: Dr. Geoffrey Modest<\/strong><\/p>\n

JAMA just published a systematic review of the literature on the use of metformin in patients with chronic kidney disease\u00a0(see\u00a0JAMA. 2014;312(24):2668-2675<\/strong>\u200b). The major concern is that metformin is renally-cleared, and that its close cousin, phenformin, was used extensively in the US, caused large numbers of cases of fatal lactic acidosis and was pulled off the market in 1977.\u00a0Major points from the systematic review:<\/p>\n

\"1024px-Metformin_500mg_Tablets\"<\/p>\n

\u00a0–65 studies identified, mostly case series and observational post-marketing surveillance but also some pharmacokinetic\/metabolic ones<\/p>\n

–though there is reduced metformin clearance with renal insufficiency,\u00a0both \u00a0metformin and\u00a0lactic acid levels are in safe ranges\u00a0in patients with eGFR of 30-60 mL\/min\/1.73m2<\/sup><\/p>\n

–the incidence of lactic acidosis in metformin users is 3-10\/100K person-years, “generally indistinguishable from the background rate”. For example,\u00a0an analysis of 347 studies of diabetics found no cases of lactic acidosis in 70,490 patient-years on metformin (nor in 55,451 in those not on metformin).<\/p>\n

–small studies which have reported “metformin lactic acidosis” have typically been in hospitalized patients with supervening illnesses precipitating metabolic decompensation (eg infection, acute kidney\/liver failure, cardiovasc collapse). Unclear if the lactic acidosis was\u00a0related to metformin. When metformin levels were\u00a0measured, they were occasionally elevated but no consistent correlation with the lactic acidosis.<\/p>\n

–observational studies suggest macrovascular benefit of metformin in patients with renal insufficiency. For example, a study of 19,691 diabetic\u00a0patients with atherosclerotic disease found that mortality rates were 6.3% in those on metformin but 9.8% in those not. \u00a0this benefit persisted in the subgroup with\u00a0eGFR of 30-60 mL\/min\/1.73m2<\/sup>. This finding\u00a0was confirmed in other observational studies<\/p>\n

–population-based\u00a0studies have found that about 25% of patients prescribed\u00a0metformin have renal dysfunction above the FDA\u00a0guidelines\u00a0(creat of >1.5 in men and >1.4 in women)….. and no clear increase in lactic acidosis.\u200b As a result of the current FDA\u00a0prohibitions, about 2.5 million people in the US would not be eligible to take metformin. \u00a0The UK guidelines are to allow metformin if\u00a0eGFR <60 mL\/min\/1.73m2<\/sup>, with recommendation to review dosing if\u00a0eGFR <45\u00a0mL\/min\/1.73m2<\/sup> and stop if\u00a0eGFR < 30\u00a0mL\/min\/1.73m2<\/sup>.<\/p>\n

–however, it should be emphasized that\u00a0no specific randomized controlled trials to check the safety of metformin in those with renal disease<\/p>\n

My sense many years ago from European data was that metformin was very rarely\u00a0associated with clinically significant\u00a0lactic acidosis in patients with renal disease. In fact\u00a0a survey\u00a0I saw\u00a0about 15 years ago in the US\u00a0showed that the majority of physicians were using metformin up to creatinines of 1.7-1.8. So, since metformin is such an important diabetes drug for many reasons (eg, improves macrovascular\/cardiac outcomes), I have been using it in men\u00a0with\u00a0creatinine of <2\u00a0and and women <1.8 \u00a0for at least 10-15 years. That being said, I usually use lower doses of metformin anyway (only marginal improvement in diabetic control\u00a0if use 2 gm\/day over 1 gm\/day), and many patients respond robustly to 500\u00a0mg (or even less, if 500 mg not tolerated). The authors of the systematic review suggest decreasing the max dose of metformin to 1000mg\/day in those with\u00a0eGFR of 30-45 mL\/min\/1.73m2<\/sup> range and not use if <30, since very\u00a0limited data do suggest an increased risk of lactic acidosis at that point.\u200b<\/p>\n","protected":false},"excerpt":{"rendered":"

Metformin in renal failure […]<\/p>\n

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