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After issuing warnings for decades about the risks of lactic acidosis in patients with chronic nephropathy, metformin is now being re-evaluated. The most recent evidence from the literature has demonstrated both a low, acceptable risk of lactic acidosis and a series of favorable effects, which go beyond its hypoglycemic activity. Patients treated with metformin show a significant mortality reduction and lower progression towards end-stage renal disease in comparison with those treated with other hypoglycemic drugs. Concerning lactic acidosis, in the last few years it has been shown how lactic acidosis almost always developed when patients kept taking the drug in the face of a concomitant\u00a0disease or situation such as sepsis, fever, diarrhea, vomiting, which reduced metformin renal clearance. Actually,\u00a0clearance of metformin is mainly renal, both by glomerular filtration and tubular secretion (apparent clearance 933\u20131317\u00a0ml\/min, half-life\u2009&amp;lt;\u20093\u00a0h). As regards treatment, in cases of lactic acidosis complicated by acute kidney injury, continuous renal replacement therapy (CRRT) plays a crucial role. Besides the elimination of metformin, CRRT \u00a0improves survival by\u00a0correcting acidosis, electrolyte alterations, and maintaining fluid balance. Lactic acidosis almost always develops because of preventable drug accumulation. Therefore, prevention is a key factor. Patients should be aware that discontinuation for a limited time does not affect their health, even when it may be inappropriate,\u00a0but it may\u00a0avoid a serious, potentially fatal adverse event.<\/jats:p>","DOI":"10.1007\/s40620-020-00941-8","type":"journal-article","created":{"date-parts":[[2020,12,29]],"date-time":"2020-12-29T03:02:43Z","timestamp":1609210963000},"page":"1127-1135","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Metformin, chronic nephropathy and lactic acidosis: a multi-faceted issue for the nephrologist"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7137-2141","authenticated-orcid":false,"given":"Filippo","family":"Mariano","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Turin, Turin, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Biancone","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, Turin, Italy 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,12,29]]},"reference":[{"key":"2026012113565749000_CR1"},{"issue":"188","key":"2026012113565749000_CR2","doi-asserted-by":"publisher","first-page":"446","DOI":"10.5694\/j.1326-5377.2008.tb01713.x","article-title":"Metformin and lactic acidosis in an Australian community setting: the fremantle diabetes study","volume":"21","author":"Kamber","year":"2008","journal-title":"Med J Aust"},{"issue":"170","key":"2026012113565749000_CR3","doi-asserted-by":"publisher","first-page":"1892","DOI":"10.1001\/archinternmed.2010.409","article-title":"Metformin use and mortality among patients with diabetes and atherothrombosis","volume":"22","author":"Roussel","year":"2010","journal-title":"Arch Intern Med"},{"issue":"4","key":"2026012113565749000_CR4","doi-asserted-by":"publisher","first-page":"e001076","DOI":"10.1136\/bmjopen-2012-001076","article-title":"Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register","volume":"13:2","author":"Ekstr\u00f6m","year":"2012","journal-title":"BMJ Open"},{"key":"2026012113565749000_CR5","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1046\/j.1464-5491.2001.00509.x 11472468","article-title":"Contraindications to metformin therapy in patients with Type 2 diabetes-a population-based study of adherence to prescribing guidelines","volume":"18","author":"Emslie-Smith","year":"2001","journal-title":"Diabet Med"},{"issue":"162","key":"2026012113565749000_CR6","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1001\/archinte.162.4.434","article-title":"Evaluation of prescribing practices: risk of lactic acidosis with metformin therapy","volume":"25","author":"Calabrese","year":"2002","journal-title":"Arch Intern Med"},{"issue":"1\u20132","key":"2026012113565749000_CR7","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1900\/RDS.2015.12.87","article-title":"Diabetic kidney disease: a syndrome rather than a single disease","volume":"12","author":"Piccoli","year":"2015","journal-title":"Rev Diabet Stud Spring-Summer"},{"key":"2026012113565749000_CR8","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1007\/s40620-020-00809-x 32725496","article-title":"Kidney and cardiovascular protection with SGLT2 inhibitors: lessons from cardiovascular outcome trials and CREDENCE","volume":"33","author":"O\u2019Hara","year":"2020","journal-title":"J Nephrol"},{"key":"2026012113565749000_CR9","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1007\/s40620-020-00738-9 32356231","article-title":"Nephroprotective effects of GLP-1 receptor agonists: where do we stand?","volume":"33","author":"Mosterd","year":"2020","journal-title":"J Nephrol"},{"key":"2026012113565749000_CR10","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1007\/s00125-019-05039-w 31853556","article-title":"2019 update to: management of hyperglycaemia in type 2 diabetes, 2018. 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