The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease
Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2...
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| Veröffentlicht in: | Diabetes care 2020-05, Vol.43 (5), p.948-955 |
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| creator | Kwon, Soie Kim, Yong Chul Park, Jae Yoon Lee, Jeonghwan An, Jung Nam Kim, Clara Tammy Oh, Sohee Park, Seokwoo Kim, Dong Ki Oh, Yun Kyu Kim, Yon Su Lim, Chun Soo Lee, Jung Pyo |
| description | Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD).
We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted.
All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73;
< 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77;
< 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276;
= 0.629).
In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice. |
| doi_str_mv | 10.2337/dc19-0936 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_journals_2393600453</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2393600453</sourcerecordid><originalsourceid>FETCH-LOGICAL-c348t-35df9396a240c2083dece2f417293399966e6add7792d674c1feefda0534d29c3</originalsourceid><addsrcrecordid>eNo9kE1LAzEQhoMotlYP_gEJePKwmmSS3c1Rav3AiiIVj0uaTOwWd7cm6aH_3i2tnoaXeXiHeQg55-xaABQ3znKdMQ35ARlyDSpTSpaHZMi41JnSWgzISYxLxpiUZXlMBiA4CMbUkLzPFkinXfuVJQwNnXiPNkXaefqCyXehqVvatfTNpBrbfvFZpwWdbVZIBb2rzRxTbelz7Vrc9DmiiXhKjrz5jni2nyPycT-ZjR-z6evD0_h2mlmQZcpAOa9B50ZIZgUrwaFF4SUvhAbQWuc55sa5otDC5YW03CN6Z5gC6YS2MCKXu95V6H7WGFO17Nah7U9WAnoZ_bcKeupqR9nQxRjQV6tQNyZsKs6qrb1qa6_a2uvZi33jet6g-yf_dMEvyxVn_Q</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2393600453</pqid></control><display><type>article</type><title>The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease</title><source>MEDLINE</source><source>EZB-FREE-00999 freely available EZB journals</source><creator>Kwon, Soie ; Kim, Yong Chul ; Park, Jae Yoon ; Lee, Jeonghwan ; An, Jung Nam ; Kim, Clara Tammy ; Oh, Sohee ; Park, Seokwoo ; Kim, Dong Ki ; Oh, Yun Kyu ; Kim, Yon Su ; Lim, Chun Soo ; Lee, Jung Pyo</creator><creatorcontrib>Kwon, Soie ; Kim, Yong Chul ; Park, Jae Yoon ; Lee, Jeonghwan ; An, Jung Nam ; Kim, Clara Tammy ; Oh, Sohee ; Park, Seokwoo ; Kim, Dong Ki ; Oh, Yun Kyu ; Kim, Yon Su ; Lim, Chun Soo ; Lee, Jung Pyo</creatorcontrib><description>Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD).
We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted.
All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73;
< 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77;
< 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276;
= 0.629).
In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.</description><identifier>ISSN: 0149-5992</identifier><identifier>EISSN: 1935-5548</identifier><identifier>DOI: 10.2337/dc19-0936</identifier><identifier>PMID: 32132005</identifier><language>eng</language><publisher>United States: American Diabetes Association</publisher><subject>Acidosis ; Acidosis, Lactic - chemically induced ; Acidosis, Lactic - epidemiology ; Aged ; Aged, 80 and over ; Antidiabetics ; Cause of Death ; Clinical trials ; Cohort Studies ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - complications ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - epidemiology ; Diabetic Nephropathies - drug therapy ; Diabetic Nephropathies - epidemiology ; Diabetic Nephropathies - pathology ; Diabetic nephropathy ; Disease Progression ; End-stage renal disease ; Female ; Health risk assessment ; Humans ; Hypoglycemic Agents - therapeutic use ; Kidney diseases ; Kidney Failure, Chronic - complications ; Kidney Failure, Chronic - epidemiology ; Kidney Failure, Chronic - mortality ; Kidneys ; Lactic acidosis ; Long-term effects ; Male ; Matching ; Metformin ; Metformin - therapeutic use ; Middle Aged ; Mortality ; Patients ; Renal Insufficiency, Chronic - complications ; Renal Insufficiency, Chronic - drug therapy ; Renal Insufficiency, Chronic - epidemiology ; Renal Insufficiency, Chronic - pathology ; Research design ; Retrospective Studies ; Risk perception ; Time Factors</subject><ispartof>Diabetes care, 2020-05, Vol.43 (5), p.948-955</ispartof><rights>2020 by the American Diabetes Association.</rights><rights>Copyright American Diabetes Association May 1, 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c348t-35df9396a240c2083dece2f417293399966e6add7792d674c1feefda0534d29c3</citedby><cites>FETCH-LOGICAL-c348t-35df9396a240c2083dece2f417293399966e6add7792d674c1feefda0534d29c3</cites><orcidid>0000-0002-4714-1260</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32132005$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kwon, Soie</creatorcontrib><creatorcontrib>Kim, Yong Chul</creatorcontrib><creatorcontrib>Park, Jae Yoon</creatorcontrib><creatorcontrib>Lee, Jeonghwan</creatorcontrib><creatorcontrib>An, Jung Nam</creatorcontrib><creatorcontrib>Kim, Clara Tammy</creatorcontrib><creatorcontrib>Oh, Sohee</creatorcontrib><creatorcontrib>Park, Seokwoo</creatorcontrib><creatorcontrib>Kim, Dong Ki</creatorcontrib><creatorcontrib>Oh, Yun Kyu</creatorcontrib><creatorcontrib>Kim, Yon Su</creatorcontrib><creatorcontrib>Lim, Chun Soo</creatorcontrib><creatorcontrib>Lee, Jung Pyo</creatorcontrib><title>The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease</title><title>Diabetes care</title><addtitle>Diabetes Care</addtitle><description>Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD).
We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted.
All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73;
< 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77;
< 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276;
= 0.629).
In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.</description><subject>Acidosis</subject><subject>Acidosis, Lactic - chemically induced</subject><subject>Acidosis, Lactic - epidemiology</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Antidiabetics</subject><subject>Cause of Death</subject><subject>Clinical trials</subject><subject>Cohort Studies</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - complications</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Diabetic Nephropathies - drug therapy</subject><subject>Diabetic Nephropathies - epidemiology</subject><subject>Diabetic Nephropathies - pathology</subject><subject>Diabetic nephropathy</subject><subject>Disease Progression</subject><subject>End-stage renal disease</subject><subject>Female</subject><subject>Health risk assessment</subject><subject>Humans</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Kidney diseases</subject><subject>Kidney Failure, Chronic - complications</subject><subject>Kidney Failure, Chronic - epidemiology</subject><subject>Kidney Failure, Chronic - mortality</subject><subject>Kidneys</subject><subject>Lactic acidosis</subject><subject>Long-term effects</subject><subject>Male</subject><subject>Matching</subject><subject>Metformin</subject><subject>Metformin - therapeutic use</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Patients</subject><subject>Renal Insufficiency, Chronic - complications</subject><subject>Renal Insufficiency, Chronic - drug therapy</subject><subject>Renal Insufficiency, Chronic - epidemiology</subject><subject>Renal Insufficiency, Chronic - pathology</subject><subject>Research design</subject><subject>Retrospective Studies</subject><subject>Risk perception</subject><subject>Time Factors</subject><issn>0149-5992</issn><issn>1935-5548</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kE1LAzEQhoMotlYP_gEJePKwmmSS3c1Rav3AiiIVj0uaTOwWd7cm6aH_3i2tnoaXeXiHeQg55-xaABQ3znKdMQ35ARlyDSpTSpaHZMi41JnSWgzISYxLxpiUZXlMBiA4CMbUkLzPFkinXfuVJQwNnXiPNkXaefqCyXehqVvatfTNpBrbfvFZpwWdbVZIBb2rzRxTbelz7Vrc9DmiiXhKjrz5jni2nyPycT-ZjR-z6evD0_h2mlmQZcpAOa9B50ZIZgUrwaFF4SUvhAbQWuc55sa5otDC5YW03CN6Z5gC6YS2MCKXu95V6H7WGFO17Nah7U9WAnoZ_bcKeupqR9nQxRjQV6tQNyZsKs6qrb1qa6_a2uvZi33jet6g-yf_dMEvyxVn_Q</recordid><startdate>202005</startdate><enddate>202005</enddate><creator>Kwon, Soie</creator><creator>Kim, Yong Chul</creator><creator>Park, Jae Yoon</creator><creator>Lee, Jeonghwan</creator><creator>An, Jung Nam</creator><creator>Kim, Clara Tammy</creator><creator>Oh, Sohee</creator><creator>Park, Seokwoo</creator><creator>Kim, Dong Ki</creator><creator>Oh, Yun Kyu</creator><creator>Kim, Yon Su</creator><creator>Lim, Chun Soo</creator><creator>Lee, Jung Pyo</creator><general>American Diabetes Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><orcidid>https://orcid.org/0000-0002-4714-1260</orcidid></search><sort><creationdate>202005</creationdate><title>The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease</title><author>Kwon, Soie ; Kim, Yong Chul ; Park, Jae Yoon ; Lee, Jeonghwan ; An, Jung Nam ; Kim, Clara Tammy ; Oh, Sohee ; Park, Seokwoo ; Kim, Dong Ki ; Oh, Yun Kyu ; Kim, Yon Su ; Lim, Chun Soo ; Lee, Jung Pyo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c348t-35df9396a240c2083dece2f417293399966e6add7792d674c1feefda0534d29c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acidosis</topic><topic>Acidosis, Lactic - chemically induced</topic><topic>Acidosis, Lactic - epidemiology</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Antidiabetics</topic><topic>Cause of Death</topic><topic>Clinical trials</topic><topic>Cohort Studies</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - complications</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Diabetic Nephropathies - drug therapy</topic><topic>Diabetic Nephropathies - epidemiology</topic><topic>Diabetic Nephropathies - pathology</topic><topic>Diabetic nephropathy</topic><topic>Disease Progression</topic><topic>End-stage renal disease</topic><topic>Female</topic><topic>Health risk assessment</topic><topic>Humans</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Kidney diseases</topic><topic>Kidney Failure, Chronic - complications</topic><topic>Kidney Failure, Chronic - epidemiology</topic><topic>Kidney Failure, Chronic - mortality</topic><topic>Kidneys</topic><topic>Lactic acidosis</topic><topic>Long-term effects</topic><topic>Male</topic><topic>Matching</topic><topic>Metformin</topic><topic>Metformin - therapeutic use</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Patients</topic><topic>Renal Insufficiency, Chronic - complications</topic><topic>Renal Insufficiency, Chronic - drug therapy</topic><topic>Renal Insufficiency, Chronic - epidemiology</topic><topic>Renal Insufficiency, Chronic - pathology</topic><topic>Research design</topic><topic>Retrospective Studies</topic><topic>Risk perception</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kwon, Soie</creatorcontrib><creatorcontrib>Kim, Yong Chul</creatorcontrib><creatorcontrib>Park, Jae Yoon</creatorcontrib><creatorcontrib>Lee, Jeonghwan</creatorcontrib><creatorcontrib>An, Jung Nam</creatorcontrib><creatorcontrib>Kim, Clara Tammy</creatorcontrib><creatorcontrib>Oh, Sohee</creatorcontrib><creatorcontrib>Park, Seokwoo</creatorcontrib><creatorcontrib>Kim, Dong Ki</creatorcontrib><creatorcontrib>Oh, Yun Kyu</creatorcontrib><creatorcontrib>Kim, Yon Su</creatorcontrib><creatorcontrib>Lim, Chun Soo</creatorcontrib><creatorcontrib>Lee, Jung Pyo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes care</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kwon, Soie</au><au>Kim, Yong Chul</au><au>Park, Jae Yoon</au><au>Lee, Jeonghwan</au><au>An, Jung Nam</au><au>Kim, Clara Tammy</au><au>Oh, Sohee</au><au>Park, Seokwoo</au><au>Kim, Dong Ki</au><au>Oh, Yun Kyu</au><au>Kim, Yon Su</au><au>Lim, Chun Soo</au><au>Lee, Jung Pyo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease</atitle><jtitle>Diabetes care</jtitle><addtitle>Diabetes Care</addtitle><date>2020-05</date><risdate>2020</risdate><volume>43</volume><issue>5</issue><spage>948</spage><epage>955</epage><pages>948-955</pages><issn>0149-5992</issn><eissn>1935-5548</eissn><abstract>Metformin is the first pharmacological option for treating type 2 diabetes. However, the use of this drug is not recommended in individuals with impaired kidney function because of the perceived risk of lactic acidosis. We aimed to assess the efficacy and safety of metformin in patients with type 2 diabetic kidney disease (DKD).
We conducted a retrospective observational cohort study of 10,426 patients with type 2 DKD from two tertiary hospitals. The primary outcomes were all-cause mortality and end-stage renal disease (ESRD) progression. The secondary outcome was metformin-associated lactic acidosis. Taking into account the possibility that patients with less severe disease were prescribed metformin, propensity score matching (PSM) was conducted.
All-cause mortality and incident ESRD were lower in the metformin group according to the multivariate Cox analysis. Because the two groups had significantly different baseline characteristics, PSM was performed. After matching, metformin usage was still associated with lower all-cause mortality (adjusted hazard ratio [aHR] 0.65; 95% CI 0.57-0.73;
< 0.001) and ESRD progression (aHR 0.67; 95% CI 0.58-0.77;
< 0.001). Only one event of metformin-associated lactic acidosis was recorded. In both the original and PSM groups, metformin usage did not increase the risk of lactic acidosis events from all causes (aHR 0.92; 95% CI 0.668-1.276;
= 0.629).
In the present retrospective study, metformin usage in advanced chronic kidney disease (CKD) patients, especially those with CKD 3B, decreased the risk of all-cause mortality and incident ESRD. Additionally, metformin did not increase the risk of lactic acidosis. However, considering the remaining biases even after PSM, further randomized controlled trials are needed to change real-world practice.</abstract><cop>United States</cop><pub>American Diabetes Association</pub><pmid>32132005</pmid><doi>10.2337/dc19-0936</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-4714-1260</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Diabetes care, 2020-05, Vol.43 (5), p.948-955 |
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| subjects | Acidosis Acidosis, Lactic - chemically induced Acidosis, Lactic - epidemiology Aged Aged, 80 and over Antidiabetics Cause of Death Clinical trials Cohort Studies Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - complications Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - epidemiology Diabetic Nephropathies - drug therapy Diabetic Nephropathies - epidemiology Diabetic Nephropathies - pathology Diabetic nephropathy Disease Progression End-stage renal disease Female Health risk assessment Humans Hypoglycemic Agents - therapeutic use Kidney diseases Kidney Failure, Chronic - complications Kidney Failure, Chronic - epidemiology Kidney Failure, Chronic - mortality Kidneys Lactic acidosis Long-term effects Male Matching Metformin Metformin - therapeutic use Middle Aged Mortality Patients Renal Insufficiency, Chronic - complications Renal Insufficiency, Chronic - drug therapy Renal Insufficiency, Chronic - epidemiology Renal Insufficiency, Chronic - pathology Research design Retrospective Studies Risk perception Time Factors |
| title | The Long-term Effects of Metformin on Patients With Type 2 Diabetic Kidney Disease |
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