Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study
Current guidance recommends against the use of metformin in people with advanced kidney impairment despite a lack of supporting evidence. The aim of this observational study was to compare outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chron...
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| Veröffentlicht in: | American journal of kidney diseases 2024-11 |
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| creator | Lambourg, Emilie J. Fu, Edouard L. McGurnaghan, Stuart Conway, Bryan R. Dhaun, Neeraj Grant, Christopher H. Pearson, Ewan R. Mark, Patrick B. Petrie, John Colhoun, Helen Bell, Samira McCrimmon, Rory Armstrong, Catherine Emslie-Smith, Alistair Lindsay, Robert MacRury, Sandra McKnight, John Pearson, Donald McKinstry, Brian |
| description | Current guidance recommends against the use of metformin in people with advanced kidney impairment despite a lack of supporting evidence. The aim of this observational study was to compare outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (eGFR |
| doi_str_mv | 10.1053/j.ajkd.2024.08.012 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_3128747055</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0272638624010412</els_id><sourcerecordid>3128747055</sourcerecordid><originalsourceid>FETCH-LOGICAL-c1529-936b0cd9d27cfb626409bca06ae2891b8e8589185154e6dd8799b986570c1b083</originalsourceid><addsrcrecordid>eNp9kE1vEzEQhi0EoqHwBzggH7ns4o-s10ZcolBa1PIhJcDR8tqT1mF3HWxvqv57nKZwrDTSSONnXnkehF5TUlPS8Hfb2mx_u5oRNq-JrAllT9CMNoxXQnL5FM0Ia1kluBQn6EVKW0KI4kI8RydcNYxypWZov8pht_PjNf4JMU0JL8OY_TgdJl8gb0Ic_IhLfTfZw5gT_uXzDV64vRktOLy8_PgeL_DX8hrGW-8Ar2zI2acbvDbxGjJeR296fDZM_T2DV3lydy_Rs43pE7x66Kfox6ez9fKiuvp2_nm5uKpsuUNV5bsdsU451tpNJ5iYE9VZQ4QBJhXtJMimdNnQZg7COdkq1SkpmpZY2hHJT9HbY-4uhj8TpKwHnyz0vRkhTElzymQ7b0nTFJQdURtDShE2ehf9YOKdpkQffOutPvjWB9-aSF18l6U3D_lTN4D7v_JPcAE-HAEoV-49RJ1s8VjU-Qg2axf8Y_l_AeJQkSA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3128747055</pqid></control><display><type>article</type><title>Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study</title><source>Access via ScienceDirect (Elsevier)</source><creator>Lambourg, Emilie J. ; Fu, Edouard L. ; McGurnaghan, Stuart ; Conway, Bryan R. ; Dhaun, Neeraj ; Grant, Christopher H. ; Pearson, Ewan R. ; Mark, Patrick B. ; Petrie, John ; Colhoun, Helen ; Bell, Samira ; McCrimmon, Rory ; Armstrong, Catherine ; Emslie-Smith, Alistair ; Lindsay, Robert ; MacRury, Sandra ; McKnight, John ; Pearson, Donald ; McKinstry, Brian</creator><creatorcontrib>Lambourg, Emilie J. ; Fu, Edouard L. ; McGurnaghan, Stuart ; Conway, Bryan R. ; Dhaun, Neeraj ; Grant, Christopher H. ; Pearson, Ewan R. ; Mark, Patrick B. ; Petrie, John ; Colhoun, Helen ; Bell, Samira ; McCrimmon, Rory ; Armstrong, Catherine ; Emslie-Smith, Alistair ; Lindsay, Robert ; MacRury, Sandra ; McKnight, John ; Pearson, Donald ; McKinstry, Brian ; Scottish Diabetes Research Network Epidemiology Group</creatorcontrib><description>Current guidance recommends against the use of metformin in people with advanced kidney impairment despite a lack of supporting evidence. The aim of this observational study was to compare outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (eGFR <30 ml/min/1.73m2).
Nationwide observational cohort study.
All adults with type 2 diabetes and incident stage 4 CKD in Scotland who were treated with metformin between January 2010 and April 2019.
Stopping versus continuing metformin within six months following incident stage 4 CKD.
Primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACE).
Target trial emulation with clone-censor-weight design and marginal structural models fit for sensitivity analyses.
In a population of 371,742 Scottish residents with a diagnosis of type 2 diabetes before 30th April 2019, 4,278 were identified as prevalent metformin users with incident CKD stage 4. Within six months of developing CKD stage IV, 1,713 (40.1%) individuals discontinued metformin. Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7%, 95% CI 60.9 to 66.6 versus 70.5%, 95% CI 68.0 to 73.0; HR=1.26, 95% CI 1.10 to 1.44), while the incidence of MACE was similar between both strategies (HR=1.05, 95% CI 0.88 to 1.26). Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR=1.34, 95% CI 1.08 to 1.67; MACE: HR=1.04, 95% CI 0.81 to 1.33).
Residual confounding.
The continued use of metformin may be appropriate when eGFR falls below 30 ml/min/1.73m2. Randomized controlled trials are needed to confirm these findings.
[Display omitted]</description><identifier>ISSN: 0272-6386</identifier><identifier>ISSN: 1523-6838</identifier><identifier>EISSN: 1523-6838</identifier><identifier>DOI: 10.1053/j.ajkd.2024.08.012</identifier><identifier>PMID: 39521399</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>chronic kidney disease ; diabetes ; epidemiology ; metformin ; target trial emulation</subject><ispartof>American journal of kidney diseases, 2024-11</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c1529-936b0cd9d27cfb626409bca06ae2891b8e8589185154e6dd8799b986570c1b083</cites><orcidid>0000-0001-9100-1575</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1053/j.ajkd.2024.08.012$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>315,781,785,3551,27929,27930,46000</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39521399$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lambourg, Emilie J.</creatorcontrib><creatorcontrib>Fu, Edouard L.</creatorcontrib><creatorcontrib>McGurnaghan, Stuart</creatorcontrib><creatorcontrib>Conway, Bryan R.</creatorcontrib><creatorcontrib>Dhaun, Neeraj</creatorcontrib><creatorcontrib>Grant, Christopher H.</creatorcontrib><creatorcontrib>Pearson, Ewan R.</creatorcontrib><creatorcontrib>Mark, Patrick B.</creatorcontrib><creatorcontrib>Petrie, John</creatorcontrib><creatorcontrib>Colhoun, Helen</creatorcontrib><creatorcontrib>Bell, Samira</creatorcontrib><creatorcontrib>McCrimmon, Rory</creatorcontrib><creatorcontrib>Armstrong, Catherine</creatorcontrib><creatorcontrib>Emslie-Smith, Alistair</creatorcontrib><creatorcontrib>Lindsay, Robert</creatorcontrib><creatorcontrib>MacRury, Sandra</creatorcontrib><creatorcontrib>McKnight, John</creatorcontrib><creatorcontrib>Pearson, Donald</creatorcontrib><creatorcontrib>McKinstry, Brian</creatorcontrib><creatorcontrib>Scottish Diabetes Research Network Epidemiology Group</creatorcontrib><title>Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study</title><title>American journal of kidney diseases</title><addtitle>Am J Kidney Dis</addtitle><description>Current guidance recommends against the use of metformin in people with advanced kidney impairment despite a lack of supporting evidence. The aim of this observational study was to compare outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (eGFR <30 ml/min/1.73m2).
Nationwide observational cohort study.
All adults with type 2 diabetes and incident stage 4 CKD in Scotland who were treated with metformin between January 2010 and April 2019.
Stopping versus continuing metformin within six months following incident stage 4 CKD.
Primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACE).
Target trial emulation with clone-censor-weight design and marginal structural models fit for sensitivity analyses.
In a population of 371,742 Scottish residents with a diagnosis of type 2 diabetes before 30th April 2019, 4,278 were identified as prevalent metformin users with incident CKD stage 4. Within six months of developing CKD stage IV, 1,713 (40.1%) individuals discontinued metformin. Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7%, 95% CI 60.9 to 66.6 versus 70.5%, 95% CI 68.0 to 73.0; HR=1.26, 95% CI 1.10 to 1.44), while the incidence of MACE was similar between both strategies (HR=1.05, 95% CI 0.88 to 1.26). Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR=1.34, 95% CI 1.08 to 1.67; MACE: HR=1.04, 95% CI 0.81 to 1.33).
Residual confounding.
The continued use of metformin may be appropriate when eGFR falls below 30 ml/min/1.73m2. Randomized controlled trials are needed to confirm these findings.
[Display omitted]</description><subject>chronic kidney disease</subject><subject>diabetes</subject><subject>epidemiology</subject><subject>metformin</subject><subject>target trial emulation</subject><issn>0272-6386</issn><issn>1523-6838</issn><issn>1523-6838</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNp9kE1vEzEQhi0EoqHwBzggH7ns4o-s10ZcolBa1PIhJcDR8tqT1mF3HWxvqv57nKZwrDTSSONnXnkehF5TUlPS8Hfb2mx_u5oRNq-JrAllT9CMNoxXQnL5FM0Ia1kluBQn6EVKW0KI4kI8RydcNYxypWZov8pht_PjNf4JMU0JL8OY_TgdJl8gb0Ic_IhLfTfZw5gT_uXzDV64vRktOLy8_PgeL_DX8hrGW-8Ar2zI2acbvDbxGjJeR296fDZM_T2DV3lydy_Rs43pE7x66Kfox6ez9fKiuvp2_nm5uKpsuUNV5bsdsU451tpNJ5iYE9VZQ4QBJhXtJMimdNnQZg7COdkq1SkpmpZY2hHJT9HbY-4uhj8TpKwHnyz0vRkhTElzymQ7b0nTFJQdURtDShE2ehf9YOKdpkQffOutPvjWB9-aSF18l6U3D_lTN4D7v_JPcAE-HAEoV-49RJ1s8VjU-Qg2axf8Y_l_AeJQkSA</recordid><startdate>20241107</startdate><enddate>20241107</enddate><creator>Lambourg, Emilie J.</creator><creator>Fu, Edouard L.</creator><creator>McGurnaghan, Stuart</creator><creator>Conway, Bryan R.</creator><creator>Dhaun, Neeraj</creator><creator>Grant, Christopher H.</creator><creator>Pearson, Ewan R.</creator><creator>Mark, Patrick B.</creator><creator>Petrie, John</creator><creator>Colhoun, Helen</creator><creator>Bell, Samira</creator><creator>McCrimmon, Rory</creator><creator>Armstrong, Catherine</creator><creator>Emslie-Smith, Alistair</creator><creator>Lindsay, Robert</creator><creator>MacRury, Sandra</creator><creator>McKnight, John</creator><creator>Pearson, Donald</creator><creator>McKinstry, Brian</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-9100-1575</orcidid></search><sort><creationdate>20241107</creationdate><title>Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study</title><author>Lambourg, Emilie J. ; 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The aim of this observational study was to compare outcomes of patients with type 2 diabetes who continued versus stopped metformin after developing stage 4 chronic kidney disease (CKD) (eGFR <30 ml/min/1.73m2).
Nationwide observational cohort study.
All adults with type 2 diabetes and incident stage 4 CKD in Scotland who were treated with metformin between January 2010 and April 2019.
Stopping versus continuing metformin within six months following incident stage 4 CKD.
Primary outcome was all-cause mortality. Secondary outcomes included major adverse cardiovascular events (MACE).
Target trial emulation with clone-censor-weight design and marginal structural models fit for sensitivity analyses.
In a population of 371,742 Scottish residents with a diagnosis of type 2 diabetes before 30th April 2019, 4,278 were identified as prevalent metformin users with incident CKD stage 4. Within six months of developing CKD stage IV, 1,713 (40.1%) individuals discontinued metformin. Compared with continuing metformin, stopping metformin was associated with a lower 3-year survival (63.7%, 95% CI 60.9 to 66.6 versus 70.5%, 95% CI 68.0 to 73.0; HR=1.26, 95% CI 1.10 to 1.44), while the incidence of MACE was similar between both strategies (HR=1.05, 95% CI 0.88 to 1.26). Marginal structural models confirmed the higher risk of all-cause mortality and similar risk of MACE in patients who stopped versus continued metformin (all-cause mortality: HR=1.34, 95% CI 1.08 to 1.67; MACE: HR=1.04, 95% CI 0.81 to 1.33).
Residual confounding.
The continued use of metformin may be appropriate when eGFR falls below 30 ml/min/1.73m2. Randomized controlled trials are needed to confirm these findings.
[Display omitted]</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>39521399</pmid><doi>10.1053/j.ajkd.2024.08.012</doi><orcidid>https://orcid.org/0000-0001-9100-1575</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
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| language | eng |
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| source | Access via ScienceDirect (Elsevier) |
| subjects | chronic kidney disease diabetes epidemiology metformin target trial emulation |
| title | Stopping Versus Continuing Metformin in Patients With Advanced CKD: A Nationwide Scottish Target Trial Emulation Study |
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