Metformin and SGLT2i as First-line Combination Therapy in Type 2 Diabetes: A Real-world Study With a Focus on Ethnicity
Suboptimal glucose control early in the diagnosis of type 2 diabetes (T2D) is strongly associated with subsequent morbidity and mortality, termed the 'glycaemic legacy'. Additionally, it is known that Asian and Black individuals are at increased risk of T2D, and its associated complication...
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| Veröffentlicht in: | Clinical therapeutics 2023-12, Vol.45 (12), p.1259-1265 |
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| creator | Anson, Matthew Zhao, Sizheng Steven Essa, Hani Austin, Philip Ibarburu, Gema Hernández Lip, Gregory Y H Alam, Uazman |
| description | Suboptimal glucose control early in the diagnosis of type 2 diabetes (T2D) is strongly associated with subsequent morbidity and mortality, termed the 'glycaemic legacy'. Additionally, it is known that Asian and Black individuals are at increased risk of T2D, and its associated complications compared to their White counterparts. However, ethnicity does not currently feature in the treatment algorithm of T2D, unlike in other cardiovascular disease states such as hypertension. We therefore sought to evaluate the real-world impact of early intensive treatment with combination therapy on cardiorenal outcomes compared to standard treatment in T2D, with a focus on ethnicity.
We performed a retrospective cohort study of all patients aged 18 or over with T2D using the TriNetX platform. TriNetX is a global collaborative network providing access to real time, anonymised medical records. We included patients who were initiated with Metformin and an SGLT2i within one month of diagnosis of T2D and compared this cohort with individuals who received Metformin only for a period of at least 1 year. We evaluated cardiovascular and renal outcomes at three years and stratified by ethnicity. We excluded individuals with a personal history of an outcome of interest.
We identified 49,651 individuals with T2D who were treated with Metformin and an SGLT2i and 1,028,806 patients with T2D who were treated with Metformin alone. A total of 98,094 individuals were included in the core analysis. The Metformin only group had a greater risk of mortality (RR 1.44, [95% CI 1.34-1.55], P |
| doi_str_mv | 10.1016/j.clinthera.2023.07.026 |
| format | Article |
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We performed a retrospective cohort study of all patients aged 18 or over with T2D using the TriNetX platform. TriNetX is a global collaborative network providing access to real time, anonymised medical records. We included patients who were initiated with Metformin and an SGLT2i within one month of diagnosis of T2D and compared this cohort with individuals who received Metformin only for a period of at least 1 year. We evaluated cardiovascular and renal outcomes at three years and stratified by ethnicity. We excluded individuals with a personal history of an outcome of interest.
We identified 49,651 individuals with T2D who were treated with Metformin and an SGLT2i and 1,028,806 patients with T2D who were treated with Metformin alone. A total of 98,094 individuals were included in the core analysis. The Metformin only group had a greater risk of mortality (RR 1.44, [95% CI 1.34-1.55], P<0.0001), CKD (RR 1.10, [95% CI 1.04-1.16], P = 0.0004), diabetic nephropathy (RR 1.06, [95% CI 1.01-1.12], P = 0.0239), heart failure (RR 1.13, [95% CI 1.07-1.21], P < 0.0001) and hospitalisation (RR 1.24, [95% CI 1.21-1.27], P < 0.0001) compared to individuals treated with Metformin and SGLT2i. Black individuals had a reduced risk of mortality (RR 0.71, [95% CI 0.55-0.92], P = 0.0099) and IHD (RR 0.73, [95% CI 0.64-0.84], P < 0.0001) compared to White individuals. Asian individuals had a reduced risk of heart failure (RR 0.61, [95% CI 0.41-0.91], P = 0.0134) and hospitalisation (RR 0.76, [95% CI 0.66-0.87], P = 0.0001) compared to White individuals.
Initial combination treatment within the first year of T2D diagnosis confers favourable cardio-metabolic outcomes when compared to standard therapy, even in patients without established cardiovascular disease. Black and Asian individuals in particular demonstrate a greater degree of benefit compared to White individuals. Further prospective studies with a focus on ethnicity are now required to validate these findings.</description><identifier>ISSN: 0149-2918</identifier><identifier>EISSN: 1879-114X</identifier><identifier>DOI: 10.1016/j.clinthera.2023.07.026</identifier><identifier>PMID: 37648574</identifier><language>eng</language><publisher>United States: Elsevier Limited</publisher><subject>Antidiabetics ; Body mass index ; Cardiovascular disease ; Cardiovascular Diseases ; Cholesterol ; Combination therapy ; Complications ; Congestive heart failure ; Core analysis ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetic nephropathy ; Diagnosis ; Diuretics ; Ethnicity ; Health services ; Heart Failure ; Humans ; Hypertension ; Hypoglycemic Agents - therapeutic use ; Ischemia ; Medical records ; Metformin ; Metformin - therapeutic use ; Minority & ethnic groups ; Morbidity ; Mortality ; Mortality risk ; Nephropathy ; Observational studies ; Patients ; Prospective Studies ; Retrospective Studies ; Risk management ; Therapy</subject><ispartof>Clinical therapeutics, 2023-12, Vol.45 (12), p.1259-1265</ispartof><rights>Copyright © 2023 Elsevier Inc. All rights reserved.</rights><rights>2023. Elsevier Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c341t-1e871abe7276d5d1b70491180ec7488adea6e67c26ba68bec710e7d39e165fc13</citedby><cites>FETCH-LOGICAL-c341t-1e871abe7276d5d1b70491180ec7488adea6e67c26ba68bec710e7d39e165fc13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37648574$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anson, Matthew</creatorcontrib><creatorcontrib>Zhao, Sizheng Steven</creatorcontrib><creatorcontrib>Essa, Hani</creatorcontrib><creatorcontrib>Austin, Philip</creatorcontrib><creatorcontrib>Ibarburu, Gema Hernández</creatorcontrib><creatorcontrib>Lip, Gregory Y H</creatorcontrib><creatorcontrib>Alam, Uazman</creatorcontrib><title>Metformin and SGLT2i as First-line Combination Therapy in Type 2 Diabetes: A Real-world Study With a Focus on Ethnicity</title><title>Clinical therapeutics</title><addtitle>Clin Ther</addtitle><description>Suboptimal glucose control early in the diagnosis of type 2 diabetes (T2D) is strongly associated with subsequent morbidity and mortality, termed the 'glycaemic legacy'. Additionally, it is known that Asian and Black individuals are at increased risk of T2D, and its associated complications compared to their White counterparts. However, ethnicity does not currently feature in the treatment algorithm of T2D, unlike in other cardiovascular disease states such as hypertension. We therefore sought to evaluate the real-world impact of early intensive treatment with combination therapy on cardiorenal outcomes compared to standard treatment in T2D, with a focus on ethnicity.
We performed a retrospective cohort study of all patients aged 18 or over with T2D using the TriNetX platform. TriNetX is a global collaborative network providing access to real time, anonymised medical records. We included patients who were initiated with Metformin and an SGLT2i within one month of diagnosis of T2D and compared this cohort with individuals who received Metformin only for a period of at least 1 year. We evaluated cardiovascular and renal outcomes at three years and stratified by ethnicity. We excluded individuals with a personal history of an outcome of interest.
We identified 49,651 individuals with T2D who were treated with Metformin and an SGLT2i and 1,028,806 patients with T2D who were treated with Metformin alone. A total of 98,094 individuals were included in the core analysis. The Metformin only group had a greater risk of mortality (RR 1.44, [95% CI 1.34-1.55], P<0.0001), CKD (RR 1.10, [95% CI 1.04-1.16], P = 0.0004), diabetic nephropathy (RR 1.06, [95% CI 1.01-1.12], P = 0.0239), heart failure (RR 1.13, [95% CI 1.07-1.21], P < 0.0001) and hospitalisation (RR 1.24, [95% CI 1.21-1.27], P < 0.0001) compared to individuals treated with Metformin and SGLT2i. Black individuals had a reduced risk of mortality (RR 0.71, [95% CI 0.55-0.92], P = 0.0099) and IHD (RR 0.73, [95% CI 0.64-0.84], P < 0.0001) compared to White individuals. Asian individuals had a reduced risk of heart failure (RR 0.61, [95% CI 0.41-0.91], P = 0.0134) and hospitalisation (RR 0.76, [95% CI 0.66-0.87], P = 0.0001) compared to White individuals.
Initial combination treatment within the first year of T2D diagnosis confers favourable cardio-metabolic outcomes when compared to standard therapy, even in patients without established cardiovascular disease. Black and Asian individuals in particular demonstrate a greater degree of benefit compared to White individuals. Further prospective studies with a focus on ethnicity are now required to validate these findings.</description><subject>Antidiabetics</subject><subject>Body mass index</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases</subject><subject>Cholesterol</subject><subject>Combination therapy</subject><subject>Complications</subject><subject>Congestive heart failure</subject><subject>Core analysis</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetic nephropathy</subject><subject>Diagnosis</subject><subject>Diuretics</subject><subject>Ethnicity</subject><subject>Health services</subject><subject>Heart Failure</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Ischemia</subject><subject>Medical records</subject><subject>Metformin</subject><subject>Metformin - therapeutic use</subject><subject>Minority & ethnic groups</subject><subject>Morbidity</subject><subject>Mortality</subject><subject>Mortality risk</subject><subject>Nephropathy</subject><subject>Observational studies</subject><subject>Patients</subject><subject>Prospective Studies</subject><subject>Retrospective Studies</subject><subject>Risk management</subject><subject>Therapy</subject><issn>0149-2918</issn><issn>1879-114X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkcFu1DAQhi0EokvhFcASFy4JHiexHW7VttsiLUKCRXCzHGdW61USL7ajKm-PVy099DSS9f_fjPwR8gFYCQzE52NpBzelAwZTcsarksmScfGCrEDJtgCo_7wkKwZ1W_AW1AV5E-ORMVa1DX9NLiopatXIekXuv2Ha-zC6iZqppz9vtzvuqIl040JMRV6CdO3Hzk0mOT_R3XnlaaE5v1tOSDm9dqbDhPELvaI_0AzFvQ9DJqW5X-hvlw7U0I23c6S5fpMOk7MuLW_Jq70ZIr57nJfk1-Zmt74rtt9vv66vtoWtakgFoJKQ-ZJL0Tc9dJLVLYBiaGWtlOnRCBTSctEZobr8CgxlX7UIotlbqC7JpwfuKfi_M8akRxctDoOZ0M9Rc9W0gjUS2hz9-Cx69HOY8nWat_nrQPL6DJQPKRt8jAH3-hTcaMKigemzG33UT2702Y1mUmc3ufn-kT93I_ZPvf8yqn_uNYyP</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Anson, Matthew</creator><creator>Zhao, Sizheng Steven</creator><creator>Essa, Hani</creator><creator>Austin, Philip</creator><creator>Ibarburu, Gema Hernández</creator><creator>Lip, Gregory Y H</creator><creator>Alam, Uazman</creator><general>Elsevier Limited</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>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>KB0</scope><scope>M0S</scope><scope>M0T</scope><scope>M1P</scope><scope>M2O</scope><scope>M7N</scope><scope>MBDVC</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope></search><sort><creationdate>202312</creationdate><title>Metformin and SGLT2i as First-line Combination Therapy in Type 2 Diabetes: A Real-world Study With a Focus on Ethnicity</title><author>Anson, Matthew ; Zhao, Sizheng Steven ; Essa, Hani ; Austin, Philip ; Ibarburu, Gema Hernández ; Lip, Gregory Y H ; Alam, Uazman</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c341t-1e871abe7276d5d1b70491180ec7488adea6e67c26ba68bec710e7d39e165fc13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Antidiabetics</topic><topic>Body mass index</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular Diseases</topic><topic>Cholesterol</topic><topic>Combination therapy</topic><topic>Complications</topic><topic>Congestive heart failure</topic><topic>Core analysis</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetic nephropathy</topic><topic>Diagnosis</topic><topic>Diuretics</topic><topic>Ethnicity</topic><topic>Health services</topic><topic>Heart Failure</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Ischemia</topic><topic>Medical records</topic><topic>Metformin</topic><topic>Metformin - therapeutic use</topic><topic>Minority & ethnic groups</topic><topic>Morbidity</topic><topic>Mortality</topic><topic>Mortality risk</topic><topic>Nephropathy</topic><topic>Observational studies</topic><topic>Patients</topic><topic>Prospective Studies</topic><topic>Retrospective Studies</topic><topic>Risk management</topic><topic>Therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anson, Matthew</creatorcontrib><creatorcontrib>Zhao, Sizheng Steven</creatorcontrib><creatorcontrib>Essa, Hani</creatorcontrib><creatorcontrib>Austin, Philip</creatorcontrib><creatorcontrib>Ibarburu, Gema Hernández</creatorcontrib><creatorcontrib>Lip, Gregory Y H</creatorcontrib><creatorcontrib>Alam, Uazman</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 Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Research Library (Corporate)</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><jtitle>Clinical therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Anson, Matthew</au><au>Zhao, Sizheng Steven</au><au>Essa, Hani</au><au>Austin, Philip</au><au>Ibarburu, Gema Hernández</au><au>Lip, Gregory Y H</au><au>Alam, Uazman</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Metformin and SGLT2i as First-line Combination Therapy in Type 2 Diabetes: A Real-world Study With a Focus on Ethnicity</atitle><jtitle>Clinical therapeutics</jtitle><addtitle>Clin Ther</addtitle><date>2023-12</date><risdate>2023</risdate><volume>45</volume><issue>12</issue><spage>1259</spage><epage>1265</epage><pages>1259-1265</pages><issn>0149-2918</issn><eissn>1879-114X</eissn><abstract>Suboptimal glucose control early in the diagnosis of type 2 diabetes (T2D) is strongly associated with subsequent morbidity and mortality, termed the 'glycaemic legacy'. Additionally, it is known that Asian and Black individuals are at increased risk of T2D, and its associated complications compared to their White counterparts. However, ethnicity does not currently feature in the treatment algorithm of T2D, unlike in other cardiovascular disease states such as hypertension. We therefore sought to evaluate the real-world impact of early intensive treatment with combination therapy on cardiorenal outcomes compared to standard treatment in T2D, with a focus on ethnicity.
We performed a retrospective cohort study of all patients aged 18 or over with T2D using the TriNetX platform. TriNetX is a global collaborative network providing access to real time, anonymised medical records. We included patients who were initiated with Metformin and an SGLT2i within one month of diagnosis of T2D and compared this cohort with individuals who received Metformin only for a period of at least 1 year. We evaluated cardiovascular and renal outcomes at three years and stratified by ethnicity. We excluded individuals with a personal history of an outcome of interest.
We identified 49,651 individuals with T2D who were treated with Metformin and an SGLT2i and 1,028,806 patients with T2D who were treated with Metformin alone. A total of 98,094 individuals were included in the core analysis. The Metformin only group had a greater risk of mortality (RR 1.44, [95% CI 1.34-1.55], P<0.0001), CKD (RR 1.10, [95% CI 1.04-1.16], P = 0.0004), diabetic nephropathy (RR 1.06, [95% CI 1.01-1.12], P = 0.0239), heart failure (RR 1.13, [95% CI 1.07-1.21], P < 0.0001) and hospitalisation (RR 1.24, [95% CI 1.21-1.27], P < 0.0001) compared to individuals treated with Metformin and SGLT2i. Black individuals had a reduced risk of mortality (RR 0.71, [95% CI 0.55-0.92], P = 0.0099) and IHD (RR 0.73, [95% CI 0.64-0.84], P < 0.0001) compared to White individuals. Asian individuals had a reduced risk of heart failure (RR 0.61, [95% CI 0.41-0.91], P = 0.0134) and hospitalisation (RR 0.76, [95% CI 0.66-0.87], P = 0.0001) compared to White individuals.
Initial combination treatment within the first year of T2D diagnosis confers favourable cardio-metabolic outcomes when compared to standard therapy, even in patients without established cardiovascular disease. Black and Asian individuals in particular demonstrate a greater degree of benefit compared to White individuals. Further prospective studies with a focus on ethnicity are now required to validate these findings.</abstract><cop>United States</cop><pub>Elsevier Limited</pub><pmid>37648574</pmid><doi>10.1016/j.clinthera.2023.07.026</doi><tpages>7</tpages></addata></record> |
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| ispartof | Clinical therapeutics, 2023-12, Vol.45 (12), p.1259-1265 |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Antidiabetics Body mass index Cardiovascular disease Cardiovascular Diseases Cholesterol Combination therapy Complications Congestive heart failure Core analysis Diabetes Diabetes mellitus Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - drug therapy Diabetic nephropathy Diagnosis Diuretics Ethnicity Health services Heart Failure Humans Hypertension Hypoglycemic Agents - therapeutic use Ischemia Medical records Metformin Metformin - therapeutic use Minority & ethnic groups Morbidity Mortality Mortality risk Nephropathy Observational studies Patients Prospective Studies Retrospective Studies Risk management Therapy |
| title | Metformin and SGLT2i as First-line Combination Therapy in Type 2 Diabetes: A Real-world Study With a Focus on Ethnicity |
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