{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:34:27Z","timestamp":1791412467503,"version":"4.3.3"},"reference-count":51,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2021,6,9]],"date-time":"2021-06-09T00:00:00Z","timestamp":1623196800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>To examine clinical and safety outcomes associated with metformin use in patients with impaired renal function.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      We searched PubMed and Embase databases from inception to August 2020, supplementing our search with a review of investigator files and reference lists of included studies. Any study reporting original data on metformin and patient\u2010centred outcomes in patients with impaired renal function, defined as an estimated glomerular filtration rate (eGFR) of less than\u200960\u2009mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      , was included. Post hoc meta\u2010analysis was performed for the outcomes of mortality, cardiovascular events and acidosis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine small prospective studies enrolling patients with significantly impaired renal function identified only one case of clinically apparent lactic acidosis. Among 13 larger retrospective studies, seven examined the risk of mortality across patient subgroups; meta\u2010analysis showed reductions in overall mortality at an eGFR of 45\u2009mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      or higher but not at an eGFR of less than 45 mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      . Eight retrospective studies evaluated acidosis as an outcome; meta\u2010analysis showed no increase in risk of acidosis except at an eGFR of less than 30\u2009mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      , in which group the HR was 1.97 (95% CI 1.03\u20133.77).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The literature shows metformin to be associated with reduced mortality and no increased risk of acidosis at an eGFR of 45\u2009mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      or higher. Metformin appears to be associated with fewer benefits and possible increases in the risk of acidosis at an eGFR of less than 30\u2009mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      . Consistent with US Food and Drug Administration guidelines, metformin should not be used at an eGFR less than 30\u2009mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      , and further research on its risk\u2010benefit profile at eGFR values approaching 30 mL\/min\/1.73m\n                      <jats:sup>2<\/jats:sup>\n                      is warranted.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.14440","type":"journal-article","created":{"date-parts":[[2021,5,19]],"date-time":"2021-05-19T11:38:55Z","timestamp":1621424335000},"page":"2035-2047","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Safety and effectiveness of metformin in patients with reduced renal function: A systematic review"],"prefix":"10.1111","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6492-7273","authenticated-orcid":false,"given":"Jeremy","family":"Orloff","sequence":"first","affiliation":[{"name":"Weill Cornell Medical College  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jea Young","family":"Min","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin","family":"Mushlin","sequence":"additional","affiliation":[{"name":"Weill Cornell Medical College  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0259-969X","authenticated-orcid":false,"given":"James","family":"Flory","sequence":"additional","affiliation":[{"name":"Memorial Sloan Kettering Cancer Center  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,6,9]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.3805"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-S009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)07037-8"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4318-z"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4337-9"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199602293340906"},{"key":"e_1_2_9_8_1","first-page":"CD002967","article-title":"Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus","volume":"4","author":"Salpeter SR","year":"2010","journal-title":"Cochrane Database Syst Rev."},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.15298"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.116.023041"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.7326\/M16-1901"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCHEARTFAILURE.112.000162"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20010042"},{"issue":"1","key":"e_1_2_9_14_1","doi-asserted-by":"crossref","first-page":"e04","DOI":"10.15171\/jnp.2020.04","article-title":"Administration of metformin in type 2 diabetes mellitus patients with chronic kidney disease; facts and myths","volume":"9","author":"Akhavan Sepahi M","year":"2020","journal-title":"J Nephropathol."},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2016.22.10.1107"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0006-341X.2000.00455.x"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.19684"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-008-0850-3"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.kisu.2017.04.001"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.3747\/pdi.2013.00048"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3747\/pdi.2015.00309"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0953-6205(02)00131-0"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc17-2231"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.03.005"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2012.01617.x"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.4103\/1319-2442.220870"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552-4604.1995.tb04033.x"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdiacomp.2019.107474"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.13206"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-2391"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/edm2.170"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.13642"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(15)00123-0"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2019.07.017"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-017-4219-3"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc19-0936"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamainternmed.2018.0292"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.119.040144"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2012-001076"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2010.02.337"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0907845"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1307684"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-018-1090-3"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12882-017-0579-5"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23387"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12764"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.i3625"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40618-018-0983-0"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc13-3023"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40471-015-0053-5"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.14414"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.2337\/dc20-2080"}],"container-title":["Diabetes, Obesity and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/dom.14440","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/dom.14440","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/pdf\/10.1111\/dom.14440","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T01:08:24Z","timestamp":1761872904000},"score":1,"resource":{"primary":{"URL":"https:\/\/dom-pubs.pericles-prod.literatumonline.com\/doi\/10.1111\/dom.14440"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,9]]},"references-count":51,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1111\/dom.14440"],"URL":"https:\/\/doi.org\/10.1111\/dom.14440","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/DOM.14440\/v3\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v3\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v1\/review3","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/DOM.14440\/v1\/review2","asserted-by":"object"}]},"ISSN":["1462-8902","1463-1326"],"issn-type":[{"value":"1462-8902","type":"print"},{"value":"1463-1326","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,9]]},"assertion":[{"value":"2021-03-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-06-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}