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Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study
Patients with low-to-normal body mass index (BMI;
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| Published in: | Cardiovascular diabetology 2024-10, Vol.23 (1), p.372-10, Article 372 |
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| container_title | Cardiovascular diabetology |
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| creator | Mori, Yuichiro Komura, Toshiaki Adomi, Motohiko Yagi, Ryuichiro Fukuma, Shingo Kondo, Naoki Yanagita, Motoko Duru, O Kenrik Tuttle, Katherine R Inoue, Kosuke |
| description | Patients with low-to-normal body mass index (BMI; |
| doi_str_mv | 10.1186/s12933-024-02478-7 |
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| fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_bcd41e39ee9544bb85db4c1b289913d3</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_bcd41e39ee9544bb85db4c1b289913d3</doaj_id><sourcerecordid>3119722760</sourcerecordid><originalsourceid>FETCH-LOGICAL-c422t-931411641d2b3949a72b1ab7ef3661fbd751df8b350e8ab5a797bc598041f3cf3</originalsourceid><addsrcrecordid>eNpVks9u1DAQxiMEoqXwAhyQj1xSMrYT21wQqqBUqsQBOFv-l11XSRxsZ5d9Hx4U76ZU7cGyxzPfb8bWV1VvobkE4N2HBFgQUjeYHhfjNXtWnQNlbY05bZ4_Op9Vr1K6axpgvIOX1RkRlHDesfPq749g_TLWm2ExITlkQo5qSnOI2UWEkZ-2XvscYkJqssioaH3YqWSWQUXkdm7KJTOGaYNmlf0p3Pu8Rfkwu6K3XmmX3aoewr7OoZ5CHNWAdLAHNKqUShPr_nxECk0FEaa9t8dBtmUGlPJiD6-rF70akntzv19Uv75--Xn1rb79fn1z9fm2NhTjXAsCFKCjYLEuLxSKYQ1KM9eTroNeW9aC7bkmbeO40q1igmnTCt5Q6InpyUV1s3JtUHdyjn5U8SCD8vJ0EeJGqpi9GZzUxlJwRDgnWkq15q3V1IDGXAgglhTWp5U1L3p01pSfiWp4An2amfxWbsJOArTQMsCF8P6eEMPvxaUsR5-MGwY1ubAkSQAEw5h1TSnFa6mJIaXo-oc-0MijV-TqFVl8Ik9ekayI3j2e8EHy3xzkHztuvvU</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3119722760</pqid></control><display><type>article</type><title>Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study</title><source>Open Access: PubMed Central</source><source>Publicly Available Content Database</source><creator>Mori, Yuichiro ; Komura, Toshiaki ; Adomi, Motohiko ; Yagi, Ryuichiro ; Fukuma, Shingo ; Kondo, Naoki ; Yanagita, Motoko ; Duru, O Kenrik ; Tuttle, Katherine R ; Inoue, Kosuke</creator><creatorcontrib>Mori, Yuichiro ; Komura, Toshiaki ; Adomi, Motohiko ; Yagi, Ryuichiro ; Fukuma, Shingo ; Kondo, Naoki ; Yanagita, Motoko ; Duru, O Kenrik ; Tuttle, Katherine R ; Inoue, Kosuke</creatorcontrib><description>Patients with low-to-normal body mass index (BMI; < 25.0 kg/m
) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials.
This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0-22.4, 22.5-24.9, 25.0-29.9, 30.0-34.9, and 35.0 ≤ kg/m
). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category.
Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m
, 1.9% [n = 5,350]; 20.0-22.4 kg/m
, 8.5% [n = 23,818]; and 22.5-24.9 kg/m
, 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m
, HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0-22.4 kg/m
, HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5-24.9 kg/m
, HR [95%CI] = 0.92 [0.84 to 1.01]).
The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors.</description><identifier>ISSN: 1475-2840</identifier><identifier>EISSN: 1475-2840</identifier><identifier>DOI: 10.1186/s12933-024-02478-7</identifier><identifier>PMID: 39438867</identifier><language>eng</language><publisher>England: BioMed Central</publisher><subject>Adult ; Aged ; Body Mass Index ; Cardiovascular Diseases - diagnosis ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - mortality ; Cardiovascular Diseases - prevention & control ; Databases, Factual ; Diabetes Mellitus, Type 2 - diagnosis ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - epidemiology ; Dipeptidyl-Peptidase IV Inhibitors - adverse effects ; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use ; Female ; Heart Disease Risk Factors ; Humans ; Incidence ; Japan - epidemiology ; Male ; Middle Aged ; Retrospective Studies ; Risk Assessment ; Risk Factors ; Sodium-Glucose Transporter 2 Inhibitors - adverse effects ; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use ; Time Factors ; Treatment Outcome</subject><ispartof>Cardiovascular diabetology, 2024-10, Vol.23 (1), p.372-10, Article 372</ispartof><rights>2024. The Author(s).</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c422t-931411641d2b3949a72b1ab7ef3661fbd751df8b350e8ab5a797bc598041f3cf3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515712/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515712/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,36990,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39438867$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mori, Yuichiro</creatorcontrib><creatorcontrib>Komura, Toshiaki</creatorcontrib><creatorcontrib>Adomi, Motohiko</creatorcontrib><creatorcontrib>Yagi, Ryuichiro</creatorcontrib><creatorcontrib>Fukuma, Shingo</creatorcontrib><creatorcontrib>Kondo, Naoki</creatorcontrib><creatorcontrib>Yanagita, Motoko</creatorcontrib><creatorcontrib>Duru, O Kenrik</creatorcontrib><creatorcontrib>Tuttle, Katherine R</creatorcontrib><creatorcontrib>Inoue, Kosuke</creatorcontrib><title>Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study</title><title>Cardiovascular diabetology</title><addtitle>Cardiovasc Diabetol</addtitle><description>Patients with low-to-normal body mass index (BMI; < 25.0 kg/m
) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials.
This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0-22.4, 22.5-24.9, 25.0-29.9, 30.0-34.9, and 35.0 ≤ kg/m
). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category.
Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m
, 1.9% [n = 5,350]; 20.0-22.4 kg/m
, 8.5% [n = 23,818]; and 22.5-24.9 kg/m
, 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m
, HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0-22.4 kg/m
, HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5-24.9 kg/m
, HR [95%CI] = 0.92 [0.84 to 1.01]).
The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors.</description><subject>Adult</subject><subject>Aged</subject><subject>Body Mass Index</subject><subject>Cardiovascular Diseases - diagnosis</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Cardiovascular Diseases - mortality</subject><subject>Cardiovascular Diseases - prevention & control</subject><subject>Databases, Factual</subject><subject>Diabetes Mellitus, Type 2 - diagnosis</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - epidemiology</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - adverse effects</subject><subject>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</subject><subject>Female</subject><subject>Heart Disease Risk Factors</subject><subject>Humans</subject><subject>Incidence</subject><subject>Japan - epidemiology</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Retrospective Studies</subject><subject>Risk Assessment</subject><subject>Risk Factors</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - adverse effects</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</subject><subject>Time Factors</subject><subject>Treatment Outcome</subject><issn>1475-2840</issn><issn>1475-2840</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpVks9u1DAQxiMEoqXwAhyQj1xSMrYT21wQqqBUqsQBOFv-l11XSRxsZ5d9Hx4U76ZU7cGyxzPfb8bWV1VvobkE4N2HBFgQUjeYHhfjNXtWnQNlbY05bZ4_Op9Vr1K6axpgvIOX1RkRlHDesfPq749g_TLWm2ExITlkQo5qSnOI2UWEkZ-2XvscYkJqssioaH3YqWSWQUXkdm7KJTOGaYNmlf0p3Pu8Rfkwu6K3XmmX3aoewr7OoZ5CHNWAdLAHNKqUShPr_nxECk0FEaa9t8dBtmUGlPJiD6-rF70akntzv19Uv75--Xn1rb79fn1z9fm2NhTjXAsCFKCjYLEuLxSKYQ1KM9eTroNeW9aC7bkmbeO40q1igmnTCt5Q6InpyUV1s3JtUHdyjn5U8SCD8vJ0EeJGqpi9GZzUxlJwRDgnWkq15q3V1IDGXAgglhTWp5U1L3p01pSfiWp4An2amfxWbsJOArTQMsCF8P6eEMPvxaUsR5-MGwY1ubAkSQAEw5h1TSnFa6mJIaXo-oc-0MijV-TqFVl8Ik9ekayI3j2e8EHy3xzkHztuvvU</recordid><startdate>20241022</startdate><enddate>20241022</enddate><creator>Mori, Yuichiro</creator><creator>Komura, Toshiaki</creator><creator>Adomi, Motohiko</creator><creator>Yagi, Ryuichiro</creator><creator>Fukuma, Shingo</creator><creator>Kondo, Naoki</creator><creator>Yanagita, Motoko</creator><creator>Duru, O Kenrik</creator><creator>Tuttle, Katherine R</creator><creator>Inoue, Kosuke</creator><general>BioMed Central</general><general>BMC</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>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20241022</creationdate><title>Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study</title><author>Mori, Yuichiro ; Komura, Toshiaki ; Adomi, Motohiko ; Yagi, Ryuichiro ; Fukuma, Shingo ; Kondo, Naoki ; Yanagita, Motoko ; Duru, O Kenrik ; Tuttle, Katherine R ; Inoue, Kosuke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c422t-931411641d2b3949a72b1ab7ef3661fbd751df8b350e8ab5a797bc598041f3cf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Body Mass Index</topic><topic>Cardiovascular Diseases - diagnosis</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Cardiovascular Diseases - mortality</topic><topic>Cardiovascular Diseases - prevention & control</topic><topic>Databases, Factual</topic><topic>Diabetes Mellitus, Type 2 - diagnosis</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - epidemiology</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - adverse effects</topic><topic>Dipeptidyl-Peptidase IV Inhibitors - therapeutic use</topic><topic>Female</topic><topic>Heart Disease Risk Factors</topic><topic>Humans</topic><topic>Incidence</topic><topic>Japan - epidemiology</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Retrospective Studies</topic><topic>Risk Assessment</topic><topic>Risk Factors</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - adverse effects</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</topic><topic>Time Factors</topic><topic>Treatment Outcome</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mori, Yuichiro</creatorcontrib><creatorcontrib>Komura, Toshiaki</creatorcontrib><creatorcontrib>Adomi, Motohiko</creatorcontrib><creatorcontrib>Yagi, Ryuichiro</creatorcontrib><creatorcontrib>Fukuma, Shingo</creatorcontrib><creatorcontrib>Kondo, Naoki</creatorcontrib><creatorcontrib>Yanagita, Motoko</creatorcontrib><creatorcontrib>Duru, O Kenrik</creatorcontrib><creatorcontrib>Tuttle, Katherine R</creatorcontrib><creatorcontrib>Inoue, Kosuke</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Cardiovascular diabetology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mori, Yuichiro</au><au>Komura, Toshiaki</au><au>Adomi, Motohiko</au><au>Yagi, Ryuichiro</au><au>Fukuma, Shingo</au><au>Kondo, Naoki</au><au>Yanagita, Motoko</au><au>Duru, O Kenrik</au><au>Tuttle, Katherine R</au><au>Inoue, Kosuke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study</atitle><jtitle>Cardiovascular diabetology</jtitle><addtitle>Cardiovasc Diabetol</addtitle><date>2024-10-22</date><risdate>2024</risdate><volume>23</volume><issue>1</issue><spage>372</spage><epage>10</epage><pages>372-10</pages><artnum>372</artnum><issn>1475-2840</issn><eissn>1475-2840</eissn><abstract>Patients with low-to-normal body mass index (BMI; < 25.0 kg/m
) were underrepresented in major randomized controlled trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors for type 2 diabetes. The present study aims to investigate the effectiveness of SGLT2 inhibitors for cardiovascular outcomes among patients with type 2 diabetes and low-to-normal BMI, using finer stratification than previous trials.
This cohort study with a target trial emulation framework was conducted using insurance claims and health screening records of more than 30 million working-age citizens in Japan acquired from April 1, 2015 to March 31, 2022. 139,783 new users of SGLT2 inhibitors matched to 139,783 users of dipeptidyl protease (DPP) 4 inhibitors with stratification by BMI category (< 20.0, 20.0-22.4, 22.5-24.9, 25.0-29.9, 30.0-34.9, and 35.0 ≤ kg/m
). The primary outcome was a composite of all-cause death, myocardial infarction, stroke, or heart failure. Secondary outcomes were the components of the primary outcome. Cox proportional hazard models were used to compare SGLT2 inhibitors with DPP4 inhibitors in the whole population and subgroups defined by the BMI category.
Among participants, 17.3% (n = 48,377) were female and 31.0% (n = 86,536) had low-to-normal BMI (< 20.0 kg/m
, 1.9% [n = 5,350]; 20.0-22.4 kg/m
, 8.5% [n = 23,818]; and 22.5-24.9 kg/m
, 20.5% [n = 57,368]). Over a median follow-up of 24 months, the primary outcome occurred in 2.9% (n = 8,165) of participants. SGLT2 inhibitors were associated with a decreased incidence of the primary outcome in the whole population (HR [95%CI] = 0.92 [0.89 to 0.96]), but not in patients with low-to-normal BMI (< 20.0 kg/m
, HR [95%CI] = 1.08 [0.80 to 1.46]; 20.0-22.4 kg/m
, HR [95%CI] = 1.04 [0.90 to 1.20]; and 22.5-24.9 kg/m
, HR [95%CI] = 0.92 [0.84 to 1.01]).
The protective effect of SGLT2 inhibitors on cardiovascular events among patients with type 2 diabetes appeared to decrease with lower BMI and was not significant among patients with low-to-normal BMI (< 25.0 kg/m2). These findings suggest the importance of considering BMI when initiating SGLT2 inhibitors.</abstract><cop>England</cop><pub>BioMed Central</pub><pmid>39438867</pmid><doi>10.1186/s12933-024-02478-7</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Cardiovascular diabetology, 2024-10, Vol.23 (1), p.372-10, Article 372 |
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| language | eng |
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| source | Open Access: PubMed Central; Publicly Available Content Database |
| subjects | Adult Aged Body Mass Index Cardiovascular Diseases - diagnosis Cardiovascular Diseases - epidemiology Cardiovascular Diseases - mortality Cardiovascular Diseases - prevention & control Databases, Factual Diabetes Mellitus, Type 2 - diagnosis Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - epidemiology Dipeptidyl-Peptidase IV Inhibitors - adverse effects Dipeptidyl-Peptidase IV Inhibitors - therapeutic use Female Heart Disease Risk Factors Humans Incidence Japan - epidemiology Male Middle Aged Retrospective Studies Risk Assessment Risk Factors Sodium-Glucose Transporter 2 Inhibitors - adverse effects Sodium-Glucose Transporter 2 Inhibitors - therapeutic use Time Factors Treatment Outcome |
| title | Sodium-glucose cotransporter 2 inhibitors and cardiovascular events among patients with type 2 diabetes and low-to-normal body mass index: a nationwide cohort study |
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