Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker
To validate pharmacodynamic responses to sodium-glucose co-transporter-2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9. Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess cl...
Gespeichert in:
Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2023-12, Vol.25 (12), p.3512-3520 |
---|---|
Hauptverfasser: | , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 3520 |
---|---|
container_issue | 12 |
container_start_page | 3512 |
container_title | Diabetes, obesity & metabolism |
container_volume | 25 |
creator | Taylor, Simeon I Cherng, Hua-Ren Shahidzadeh Yazdi, Zhinous Montasser, May E Whitlatch, Hilary B Mitchell, Braxton D Shuldiner, Alan R Streeten, Elizabeth A Beitelshees, Amber L |
description | To validate pharmacodynamic responses to sodium-glucose co-transporter-2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9.
Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug-induced increases in urinary excretion of glucose, sodium and uric acid.
This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (-4.1 mg/dL; P = 6 × 10
), serum creatinine (+0.05 mg/dL; P = 8 × 10
) and serum uric acid (-0.90 mg/dL; P = 5 × 10
). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ~60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram-creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated glomerular filtration rate or age in those healthy individuals without diabetes with an estimated glomerular filtration rate of more than 60 mL/min/1.73m
.
Normalizing data relative to creatinine excretion will facilitate including data from males and females in a single analysis. Furthermore, because our ongoing pharmacogenomic study (NCT02891954) is conducted in healthy individuals, this will facilitate detection of genetic associations with limited confounding by other factors such as HbA1c and renal function. |
doi_str_mv | 10.1111/dom.15246 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2856318650</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2856318650</sourcerecordid><originalsourceid>FETCH-LOGICAL-c313t-460b372be87574bcf982111a9b4a7d9ca70d4e77113f2e811692efef47735fd3</originalsourceid><addsrcrecordid>eNpdkU1LxDAQhoMofh_8A1Lwoodovtqk3mTxCwQ9LF5LmkzXaNvUpBX33xvX1YNzmRl45mVmXoSOKDmnKS6s785pzkSxgXapKDimnBWbq5phVRK2g_ZifCWECK7kNtrhsiBKSLqLPp5edOi08QvoYXQmZr7Jordu6vCinYyPkBmPx6D7OPgwQsAsc_2Lq93oQ7zMnnXrrB6d778ndRbhE-tF72MSy4a1uF32ukt97XynwxuEA7TV6DbC4Trvo_nN9Xx2hx8eb-9nVw_YcMpHLApSc8lqUDKXojZNqVg6WJe10NKWRktiBUhJKW8YKEqLkkEDjZCS543l--j0R3YI_n2COFadiwbaVvfgp1gxlRecqiInCT35h776KfRpuUQpKWWuCE3U2Q9lgo8xQFMNwaWTlhUl1bcXVfKiWnmR2OO14lR3YP_I3-fzLzvphaY</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2887775801</pqid></control><display><type>article</type><title>Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><creator>Taylor, Simeon I ; Cherng, Hua-Ren ; Shahidzadeh Yazdi, Zhinous ; Montasser, May E ; Whitlatch, Hilary B ; Mitchell, Braxton D ; Shuldiner, Alan R ; Streeten, Elizabeth A ; Beitelshees, Amber L</creator><creatorcontrib>Taylor, Simeon I ; Cherng, Hua-Ren ; Shahidzadeh Yazdi, Zhinous ; Montasser, May E ; Whitlatch, Hilary B ; Mitchell, Braxton D ; Shuldiner, Alan R ; Streeten, Elizabeth A ; Beitelshees, Amber L</creatorcontrib><description>To validate pharmacodynamic responses to sodium-glucose co-transporter-2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9.
Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug-induced increases in urinary excretion of glucose, sodium and uric acid.
This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (-4.1 mg/dL; P = 6 × 10
), serum creatinine (+0.05 mg/dL; P = 8 × 10
) and serum uric acid (-0.90 mg/dL; P = 5 × 10
). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ~60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram-creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated glomerular filtration rate or age in those healthy individuals without diabetes with an estimated glomerular filtration rate of more than 60 mL/min/1.73m
.
Normalizing data relative to creatinine excretion will facilitate including data from males and females in a single analysis. Furthermore, because our ongoing pharmacogenomic study (NCT02891954) is conducted in healthy individuals, this will facilitate detection of genetic associations with limited confounding by other factors such as HbA1c and renal function.</description><identifier>ISSN: 1462-8902</identifier><identifier>ISSN: 1463-1326</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.15246</identifier><identifier>PMID: 37608471</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Biomarkers ; Blood Glucose ; Canagliflozin ; Creatinine ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - genetics ; Excretion ; Fasting ; Female ; Genetic diversity ; Glomerular Filtration Rate ; Glucose ; Glucose - pharmacology ; Glucose transporter ; Glucosides - pharmacology ; Glycosuria ; Humans ; Hypoglycemic Agents - pharmacology ; Hypoglycemic Agents - therapeutic use ; Male ; Males ; Pharmacodynamics ; Pharmacogenetics ; Pharmacogenomics ; Pilot Projects ; Precision medicine ; Renal function ; Sodium ; Sodium-Glucose Transporter 2 Inhibitors - pharmacology ; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use ; Symporters - pharmacology ; Uric Acid</subject><ispartof>Diabetes, obesity & metabolism, 2023-12, Vol.25 (12), p.3512-3520</ispartof><rights>2023 John Wiley & Sons Ltd.</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c313t-460b372be87574bcf982111a9b4a7d9ca70d4e77113f2e811692efef47735fd3</citedby><cites>FETCH-LOGICAL-c313t-460b372be87574bcf982111a9b4a7d9ca70d4e77113f2e811692efef47735fd3</cites><orcidid>0000-0001-7500-7854</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/37608471$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Taylor, Simeon I</creatorcontrib><creatorcontrib>Cherng, Hua-Ren</creatorcontrib><creatorcontrib>Shahidzadeh Yazdi, Zhinous</creatorcontrib><creatorcontrib>Montasser, May E</creatorcontrib><creatorcontrib>Whitlatch, Hilary B</creatorcontrib><creatorcontrib>Mitchell, Braxton D</creatorcontrib><creatorcontrib>Shuldiner, Alan R</creatorcontrib><creatorcontrib>Streeten, Elizabeth A</creatorcontrib><creatorcontrib>Beitelshees, Amber L</creatorcontrib><title>Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker</title><title>Diabetes, obesity & metabolism</title><addtitle>Diabetes Obes Metab</addtitle><description>To validate pharmacodynamic responses to sodium-glucose co-transporter-2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9.
Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug-induced increases in urinary excretion of glucose, sodium and uric acid.
This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (-4.1 mg/dL; P = 6 × 10
), serum creatinine (+0.05 mg/dL; P = 8 × 10
) and serum uric acid (-0.90 mg/dL; P = 5 × 10
). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ~60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram-creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated glomerular filtration rate or age in those healthy individuals without diabetes with an estimated glomerular filtration rate of more than 60 mL/min/1.73m
.
Normalizing data relative to creatinine excretion will facilitate including data from males and females in a single analysis. Furthermore, because our ongoing pharmacogenomic study (NCT02891954) is conducted in healthy individuals, this will facilitate detection of genetic associations with limited confounding by other factors such as HbA1c and renal function.</description><subject>Biomarkers</subject><subject>Blood Glucose</subject><subject>Canagliflozin</subject><subject>Creatinine</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Excretion</subject><subject>Fasting</subject><subject>Female</subject><subject>Genetic diversity</subject><subject>Glomerular Filtration Rate</subject><subject>Glucose</subject><subject>Glucose - pharmacology</subject><subject>Glucose transporter</subject><subject>Glucosides - pharmacology</subject><subject>Glycosuria</subject><subject>Humans</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>Hypoglycemic Agents - therapeutic use</subject><subject>Male</subject><subject>Males</subject><subject>Pharmacodynamics</subject><subject>Pharmacogenetics</subject><subject>Pharmacogenomics</subject><subject>Pilot Projects</subject><subject>Precision medicine</subject><subject>Renal function</subject><subject>Sodium</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</subject><subject>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</subject><subject>Symporters - pharmacology</subject><subject>Uric Acid</subject><issn>1462-8902</issn><issn>1463-1326</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkU1LxDAQhoMofh_8A1Lwoodovtqk3mTxCwQ9LF5LmkzXaNvUpBX33xvX1YNzmRl45mVmXoSOKDmnKS6s785pzkSxgXapKDimnBWbq5phVRK2g_ZifCWECK7kNtrhsiBKSLqLPp5edOi08QvoYXQmZr7Jordu6vCinYyPkBmPx6D7OPgwQsAsc_2Lq93oQ7zMnnXrrB6d778ndRbhE-tF72MSy4a1uF32ukt97XynwxuEA7TV6DbC4Trvo_nN9Xx2hx8eb-9nVw_YcMpHLApSc8lqUDKXojZNqVg6WJe10NKWRktiBUhJKW8YKEqLkkEDjZCS543l--j0R3YI_n2COFadiwbaVvfgp1gxlRecqiInCT35h776KfRpuUQpKWWuCE3U2Q9lgo8xQFMNwaWTlhUl1bcXVfKiWnmR2OO14lR3YP_I3-fzLzvphaY</recordid><startdate>202312</startdate><enddate>202312</enddate><creator>Taylor, Simeon I</creator><creator>Cherng, Hua-Ren</creator><creator>Shahidzadeh Yazdi, Zhinous</creator><creator>Montasser, May E</creator><creator>Whitlatch, Hilary B</creator><creator>Mitchell, Braxton D</creator><creator>Shuldiner, Alan R</creator><creator>Streeten, Elizabeth A</creator><creator>Beitelshees, Amber L</creator><general>Wiley Subscription Services, Inc</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>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-7500-7854</orcidid></search><sort><creationdate>202312</creationdate><title>Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker</title><author>Taylor, Simeon I ; Cherng, Hua-Ren ; Shahidzadeh Yazdi, Zhinous ; Montasser, May E ; Whitlatch, Hilary B ; Mitchell, Braxton D ; Shuldiner, Alan R ; Streeten, Elizabeth A ; Beitelshees, Amber L</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c313t-460b372be87574bcf982111a9b4a7d9ca70d4e77113f2e811692efef47735fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Biomarkers</topic><topic>Blood Glucose</topic><topic>Canagliflozin</topic><topic>Creatinine</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Excretion</topic><topic>Fasting</topic><topic>Female</topic><topic>Genetic diversity</topic><topic>Glomerular Filtration Rate</topic><topic>Glucose</topic><topic>Glucose - pharmacology</topic><topic>Glucose transporter</topic><topic>Glucosides - pharmacology</topic><topic>Glycosuria</topic><topic>Humans</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>Hypoglycemic Agents - therapeutic use</topic><topic>Male</topic><topic>Males</topic><topic>Pharmacodynamics</topic><topic>Pharmacogenetics</topic><topic>Pharmacogenomics</topic><topic>Pilot Projects</topic><topic>Precision medicine</topic><topic>Renal function</topic><topic>Sodium</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - pharmacology</topic><topic>Sodium-Glucose Transporter 2 Inhibitors - therapeutic use</topic><topic>Symporters - pharmacology</topic><topic>Uric Acid</topic><toplevel>online_resources</toplevel><creatorcontrib>Taylor, Simeon I</creatorcontrib><creatorcontrib>Cherng, Hua-Ren</creatorcontrib><creatorcontrib>Shahidzadeh Yazdi, Zhinous</creatorcontrib><creatorcontrib>Montasser, May E</creatorcontrib><creatorcontrib>Whitlatch, Hilary B</creatorcontrib><creatorcontrib>Mitchell, Braxton D</creatorcontrib><creatorcontrib>Shuldiner, Alan R</creatorcontrib><creatorcontrib>Streeten, Elizabeth A</creatorcontrib><creatorcontrib>Beitelshees, Amber L</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Taylor, Simeon I</au><au>Cherng, Hua-Ren</au><au>Shahidzadeh Yazdi, Zhinous</au><au>Montasser, May E</au><au>Whitlatch, Hilary B</au><au>Mitchell, Braxton D</au><au>Shuldiner, Alan R</au><au>Streeten, Elizabeth A</au><au>Beitelshees, Amber L</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><addtitle>Diabetes Obes Metab</addtitle><date>2023-12</date><risdate>2023</risdate><volume>25</volume><issue>12</issue><spage>3512</spage><epage>3520</epage><pages>3512-3520</pages><issn>1462-8902</issn><issn>1463-1326</issn><eissn>1463-1326</eissn><abstract>To validate pharmacodynamic responses to sodium-glucose co-transporter-2 (SGLT2) inhibitors and test for association with genetic variants in SLC5A4, SLC5A9, and SLC2A9.
Canagliflozin (300 mg), a SGLT2 inhibitor, was administered to 30 healthy volunteers. Several endpoints were measured to assess clinically relevant responses, including drug-induced increases in urinary excretion of glucose, sodium and uric acid.
This pilot study confirmed that canagliflozin (300 mg) triggered acute changes in mean levels of several biomarkers: fasting plasma glucose (-4.1 mg/dL; P = 6 × 10
), serum creatinine (+0.05 mg/dL; P = 8 × 10
) and serum uric acid (-0.90 mg/dL; P = 5 × 10
). The effects of sex on glucosuria depended upon how data were normalized. Whereas males' responses were ~60% greater when data were normalized to body surface area, males and females exhibited similar responses when glucosuria was expressed as grams of urinary glucose per gram-creatinine. The magnitude of glucosuria was not significantly correlated with fasting plasma glucose, estimated glomerular filtration rate or age in those healthy individuals without diabetes with an estimated glomerular filtration rate of more than 60 mL/min/1.73m
.
Normalizing data relative to creatinine excretion will facilitate including data from males and females in a single analysis. Furthermore, because our ongoing pharmacogenomic study (NCT02891954) is conducted in healthy individuals, this will facilitate detection of genetic associations with limited confounding by other factors such as HbA1c and renal function.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37608471</pmid><doi>10.1111/dom.15246</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0001-7500-7854</orcidid></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1462-8902 |
ispartof | Diabetes, obesity & metabolism, 2023-12, Vol.25 (12), p.3512-3520 |
issn | 1462-8902 1463-1326 1463-1326 |
language | eng |
recordid | cdi_proquest_miscellaneous_2856318650 |
source | MEDLINE; Access via Wiley Online Library |
subjects | Biomarkers Blood Glucose Canagliflozin Creatinine Diabetes Diabetes mellitus Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - genetics Excretion Fasting Female Genetic diversity Glomerular Filtration Rate Glucose Glucose - pharmacology Glucose transporter Glucosides - pharmacology Glycosuria Humans Hypoglycemic Agents - pharmacology Hypoglycemic Agents - therapeutic use Male Males Pharmacodynamics Pharmacogenetics Pharmacogenomics Pilot Projects Precision medicine Renal function Sodium Sodium-Glucose Transporter 2 Inhibitors - pharmacology Sodium-Glucose Transporter 2 Inhibitors - therapeutic use Symporters - pharmacology Uric Acid |
title | Pharmacogenetics of sodium-glucose co-transporter-2 inhibitors: Validation of a sex-agnostic pharmacodynamic biomarker |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-26T19%3A45%3A26IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Pharmacogenetics%20of%20sodium-glucose%20co-transporter-2%20inhibitors:%20Validation%20of%20a%20sex-agnostic%20pharmacodynamic%20biomarker&rft.jtitle=Diabetes,%20obesity%20&%20metabolism&rft.au=Taylor,%20Simeon%20I&rft.date=2023-12&rft.volume=25&rft.issue=12&rft.spage=3512&rft.epage=3520&rft.pages=3512-3520&rft.issn=1462-8902&rft.eissn=1463-1326&rft_id=info:doi/10.1111/dom.15246&rft_dat=%3Cproquest_cross%3E2856318650%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2887775801&rft_id=info:pmid/37608471&rfr_iscdi=true |