Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial
Introduction We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus. Methods Patients (baseline mean [standard deviation] glycated hemoglobin 7.91...
Gespeichert in:
| Veröffentlicht in: | Advances in therapy 2019-10, Vol.36 (10), p.2769-2782 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2782 |
|---|---|
| container_issue | 10 |
| container_start_page | 2769 |
| container_title | Advances in therapy |
| container_volume | 36 |
| creator | Nishimura, Rimei Tanaka, Yuko Koiwai, Kazuki Ishida, Kosuke Salsali, Afshin Kaspers, Stefan Kohler, Sven Lund, Søren S. |
| description | Introduction
We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus.
Methods
Patients (baseline mean [standard deviation] glycated hemoglobin 7.91% [0.80%]; body mass index 24.3 [3.2] kg/m
2
) were randomized to empagliflozin 10 mg (
n
= 20), empagliflozin 25 mg (
n
= 19), or placebo (
n
= 21) daily as monotherapy for 28 days. Meal tolerance tests (MTTs; breakfast, lunch, dinner) were performed on day − 1, day 1 (first day of treatment), and day 28. On day 1 and day 28, study drug was administered 1 h before breakfast. Free fatty acids and blood ketone bodies were measured before and 1, 2, and 3 h after each MTT, and the next morning (overnight fast).
Results
Empagliflozin significantly reduced plasma glucose and insulin and reduced body weight vs. placebo. Empagliflozin increased free fatty acids and total ketones bodies at day 1 and day 28. At day 28, the adjusted mean (95% confidence interval) difference vs. placebo in the time-corrected area under curve over 24 h for total ketone bodies was 67.1 (12.3, 121.8) µmol·h/L·h (
P
= 0.017) with empagliflozin 10 mg and 178.1 (123.9, 232.2) µmol·h/L·h (
P
|
| doi_str_mv | 10.1007/s12325-019-01045-x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2301882990</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2301882990</sourcerecordid><originalsourceid>FETCH-LOGICAL-c347t-9499377e3c1d54326eafe361fedab5250757084b62463a77f20daec31937cc0c3</originalsourceid><addsrcrecordid>eNp9kc2O0zAUhS0EYsrAC7BAd8km4L_ECbtSWv4GgVCR2Fmucz14lMTBdsR0XoJXxtCBJYsrW_J3ju7xIeQxo88Ypep5YlzwuqKsK0NlXV3fISvWNnVVht8lK6okq7hov56RByldUcqpqtv75EwwKaWizYr83DqHNkNwsB1nczl4N4QbP0GYYBcRYWdyPsLa-j6BmXp4jzlMCC9D7zFBAd-Z2UyYED6Z7HHKCX74_A32xxmBwytvDpgL-QGHweclvYA1fC5GYfQ32MMmTDmGYSjXffRmeEjuOTMkfHR7npMvu-1-86a6-Pj67WZ9UVkhVa462XVCKRSW9bUUvEHjUDTMYW8ONa9LTkVbeWi4bIRRynHaG7SCFZW11Ipz8vTkO8fwfcGU9eiTLTuWLGFJmgvK2pZ3HS0oP6E2hpQiOj1HP5p41Izq30XoUxG6FKH_FKGvi-jJrf9yGLH_J_n78wUQJyCVp-kSo74KS5xK5v_Z_gKwRJRm</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2301882990</pqid></control><display><type>article</type><title>Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial</title><source>SpringerLink Journals</source><creator>Nishimura, Rimei ; Tanaka, Yuko ; Koiwai, Kazuki ; Ishida, Kosuke ; Salsali, Afshin ; Kaspers, Stefan ; Kohler, Sven ; Lund, Søren S.</creator><creatorcontrib>Nishimura, Rimei ; Tanaka, Yuko ; Koiwai, Kazuki ; Ishida, Kosuke ; Salsali, Afshin ; Kaspers, Stefan ; Kohler, Sven ; Lund, Søren S.</creatorcontrib><description>Introduction
We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus.
Methods
Patients (baseline mean [standard deviation] glycated hemoglobin 7.91% [0.80%]; body mass index 24.3 [3.2] kg/m
2
) were randomized to empagliflozin 10 mg (
n
= 20), empagliflozin 25 mg (
n
= 19), or placebo (
n
= 21) daily as monotherapy for 28 days. Meal tolerance tests (MTTs; breakfast, lunch, dinner) were performed on day − 1, day 1 (first day of treatment), and day 28. On day 1 and day 28, study drug was administered 1 h before breakfast. Free fatty acids and blood ketone bodies were measured before and 1, 2, and 3 h after each MTT, and the next morning (overnight fast).
Results
Empagliflozin significantly reduced plasma glucose and insulin and reduced body weight vs. placebo. Empagliflozin increased free fatty acids and total ketones bodies at day 1 and day 28. At day 28, the adjusted mean (95% confidence interval) difference vs. placebo in the time-corrected area under curve over 24 h for total ketone bodies was 67.1 (12.3, 121.8) µmol·h/L·h (
P
= 0.017) with empagliflozin 10 mg and 178.1 (123.9, 232.2) µmol·h/L·h (
P
< 0.001) with empagliflozin 25 mg. Increases in ketones with empagliflozin vs. placebo peaked just before and declined after meals, with the highest peak before breakfast. Changes in total ketone bodies appeared to be associated with changes in plasma glucose, insulin, and free fatty acids.
Conclusion
Empagliflozin modestly increased free fatty acids and blood ketone bodies after a single dose and 28 days’ treatment. Increases in ketones appeared to be related to the duration of fasting and were most pronounced before breakfast. Increases in ketones appeared to be associated with changes in well-known metabolic determinants of ketone production.
Trial Registration
ClinicalTrials.gov identifier, NCT01947855.
Funding
Boehringer Ingelheim & Eli Lilly and Company.</description><identifier>ISSN: 0741-238X</identifier><identifier>EISSN: 1865-8652</identifier><identifier>DOI: 10.1007/s12325-019-01045-x</identifier><identifier>PMID: 31444706</identifier><language>eng</language><publisher>Cheshire: Springer Healthcare</publisher><subject>Cardiology ; Endocrinology ; Health technology assessment ; Internal Medicine ; Medicine ; Medicine & Public Health ; Oncology ; Original Research ; Pharmacology/Toxicology ; Rheumatology</subject><ispartof>Advances in therapy, 2019-10, Vol.36 (10), p.2769-2782</ispartof><rights>Springer Healthcare Ltd., part of Springer Nature 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c347t-9499377e3c1d54326eafe361fedab5250757084b62463a77f20daec31937cc0c3</citedby><cites>FETCH-LOGICAL-c347t-9499377e3c1d54326eafe361fedab5250757084b62463a77f20daec31937cc0c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12325-019-01045-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12325-019-01045-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31444706$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Nishimura, Rimei</creatorcontrib><creatorcontrib>Tanaka, Yuko</creatorcontrib><creatorcontrib>Koiwai, Kazuki</creatorcontrib><creatorcontrib>Ishida, Kosuke</creatorcontrib><creatorcontrib>Salsali, Afshin</creatorcontrib><creatorcontrib>Kaspers, Stefan</creatorcontrib><creatorcontrib>Kohler, Sven</creatorcontrib><creatorcontrib>Lund, Søren S.</creatorcontrib><title>Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial</title><title>Advances in therapy</title><addtitle>Adv Ther</addtitle><addtitle>Adv Ther</addtitle><description>Introduction
We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus.
Methods
Patients (baseline mean [standard deviation] glycated hemoglobin 7.91% [0.80%]; body mass index 24.3 [3.2] kg/m
2
) were randomized to empagliflozin 10 mg (
n
= 20), empagliflozin 25 mg (
n
= 19), or placebo (
n
= 21) daily as monotherapy for 28 days. Meal tolerance tests (MTTs; breakfast, lunch, dinner) were performed on day − 1, day 1 (first day of treatment), and day 28. On day 1 and day 28, study drug was administered 1 h before breakfast. Free fatty acids and blood ketone bodies were measured before and 1, 2, and 3 h after each MTT, and the next morning (overnight fast).
Results
Empagliflozin significantly reduced plasma glucose and insulin and reduced body weight vs. placebo. Empagliflozin increased free fatty acids and total ketones bodies at day 1 and day 28. At day 28, the adjusted mean (95% confidence interval) difference vs. placebo in the time-corrected area under curve over 24 h for total ketone bodies was 67.1 (12.3, 121.8) µmol·h/L·h (
P
= 0.017) with empagliflozin 10 mg and 178.1 (123.9, 232.2) µmol·h/L·h (
P
< 0.001) with empagliflozin 25 mg. Increases in ketones with empagliflozin vs. placebo peaked just before and declined after meals, with the highest peak before breakfast. Changes in total ketone bodies appeared to be associated with changes in plasma glucose, insulin, and free fatty acids.
Conclusion
Empagliflozin modestly increased free fatty acids and blood ketone bodies after a single dose and 28 days’ treatment. Increases in ketones appeared to be related to the duration of fasting and were most pronounced before breakfast. Increases in ketones appeared to be associated with changes in well-known metabolic determinants of ketone production.
Trial Registration
ClinicalTrials.gov identifier, NCT01947855.
Funding
Boehringer Ingelheim & Eli Lilly and Company.</description><subject>Cardiology</subject><subject>Endocrinology</subject><subject>Health technology assessment</subject><subject>Internal Medicine</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Oncology</subject><subject>Original Research</subject><subject>Pharmacology/Toxicology</subject><subject>Rheumatology</subject><issn>0741-238X</issn><issn>1865-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kc2O0zAUhS0EYsrAC7BAd8km4L_ECbtSWv4GgVCR2Fmucz14lMTBdsR0XoJXxtCBJYsrW_J3ju7xIeQxo88Ypep5YlzwuqKsK0NlXV3fISvWNnVVht8lK6okq7hov56RByldUcqpqtv75EwwKaWizYr83DqHNkNwsB1nczl4N4QbP0GYYBcRYWdyPsLa-j6BmXp4jzlMCC9D7zFBAd-Z2UyYED6Z7HHKCX74_A32xxmBwytvDpgL-QGHweclvYA1fC5GYfQ32MMmTDmGYSjXffRmeEjuOTMkfHR7npMvu-1-86a6-Pj67WZ9UVkhVa462XVCKRSW9bUUvEHjUDTMYW8ONa9LTkVbeWi4bIRRynHaG7SCFZW11Ipz8vTkO8fwfcGU9eiTLTuWLGFJmgvK2pZ3HS0oP6E2hpQiOj1HP5p41Izq30XoUxG6FKH_FKGvi-jJrf9yGLH_J_n78wUQJyCVp-kSo74KS5xK5v_Z_gKwRJRm</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Nishimura, Rimei</creator><creator>Tanaka, Yuko</creator><creator>Koiwai, Kazuki</creator><creator>Ishida, Kosuke</creator><creator>Salsali, Afshin</creator><creator>Kaspers, Stefan</creator><creator>Kohler, Sven</creator><creator>Lund, Søren S.</creator><general>Springer Healthcare</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20191001</creationdate><title>Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial</title><author>Nishimura, Rimei ; Tanaka, Yuko ; Koiwai, Kazuki ; Ishida, Kosuke ; Salsali, Afshin ; Kaspers, Stefan ; Kohler, Sven ; Lund, Søren S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c347t-9499377e3c1d54326eafe361fedab5250757084b62463a77f20daec31937cc0c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Cardiology</topic><topic>Endocrinology</topic><topic>Health technology assessment</topic><topic>Internal Medicine</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Oncology</topic><topic>Original Research</topic><topic>Pharmacology/Toxicology</topic><topic>Rheumatology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Nishimura, Rimei</creatorcontrib><creatorcontrib>Tanaka, Yuko</creatorcontrib><creatorcontrib>Koiwai, Kazuki</creatorcontrib><creatorcontrib>Ishida, Kosuke</creatorcontrib><creatorcontrib>Salsali, Afshin</creatorcontrib><creatorcontrib>Kaspers, Stefan</creatorcontrib><creatorcontrib>Kohler, Sven</creatorcontrib><creatorcontrib>Lund, Søren S.</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Advances in therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Nishimura, Rimei</au><au>Tanaka, Yuko</au><au>Koiwai, Kazuki</au><au>Ishida, Kosuke</au><au>Salsali, Afshin</au><au>Kaspers, Stefan</au><au>Kohler, Sven</au><au>Lund, Søren S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial</atitle><jtitle>Advances in therapy</jtitle><stitle>Adv Ther</stitle><addtitle>Adv Ther</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>36</volume><issue>10</issue><spage>2769</spage><epage>2782</epage><pages>2769-2782</pages><issn>0741-238X</issn><eissn>1865-8652</eissn><abstract>Introduction
We report a randomized, double-blind, placebo-controlled, 4-week study to investigate the effect of empagliflozin on free fatty acids and blood ketone bodies in Japanese patients with type 2 diabetes mellitus.
Methods
Patients (baseline mean [standard deviation] glycated hemoglobin 7.91% [0.80%]; body mass index 24.3 [3.2] kg/m
2
) were randomized to empagliflozin 10 mg (
n
= 20), empagliflozin 25 mg (
n
= 19), or placebo (
n
= 21) daily as monotherapy for 28 days. Meal tolerance tests (MTTs; breakfast, lunch, dinner) were performed on day − 1, day 1 (first day of treatment), and day 28. On day 1 and day 28, study drug was administered 1 h before breakfast. Free fatty acids and blood ketone bodies were measured before and 1, 2, and 3 h after each MTT, and the next morning (overnight fast).
Results
Empagliflozin significantly reduced plasma glucose and insulin and reduced body weight vs. placebo. Empagliflozin increased free fatty acids and total ketones bodies at day 1 and day 28. At day 28, the adjusted mean (95% confidence interval) difference vs. placebo in the time-corrected area under curve over 24 h for total ketone bodies was 67.1 (12.3, 121.8) µmol·h/L·h (
P
= 0.017) with empagliflozin 10 mg and 178.1 (123.9, 232.2) µmol·h/L·h (
P
< 0.001) with empagliflozin 25 mg. Increases in ketones with empagliflozin vs. placebo peaked just before and declined after meals, with the highest peak before breakfast. Changes in total ketone bodies appeared to be associated with changes in plasma glucose, insulin, and free fatty acids.
Conclusion
Empagliflozin modestly increased free fatty acids and blood ketone bodies after a single dose and 28 days’ treatment. Increases in ketones appeared to be related to the duration of fasting and were most pronounced before breakfast. Increases in ketones appeared to be associated with changes in well-known metabolic determinants of ketone production.
Trial Registration
ClinicalTrials.gov identifier, NCT01947855.
Funding
Boehringer Ingelheim & Eli Lilly and Company.</abstract><cop>Cheshire</cop><pub>Springer Healthcare</pub><pmid>31444706</pmid><doi>10.1007/s12325-019-01045-x</doi><tpages>14</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0741-238X |
| ispartof | Advances in therapy, 2019-10, Vol.36 (10), p.2769-2782 |
| issn | 0741-238X 1865-8652 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_2301882990 |
| source | SpringerLink Journals |
| subjects | Cardiology Endocrinology Health technology assessment Internal Medicine Medicine Medicine & Public Health Oncology Original Research Pharmacology/Toxicology Rheumatology |
| title | Effect of Empagliflozin on Free Fatty Acids and Ketone Bodies in Japanese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-15T05%3A19%3A43IST&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=Effect%20of%20Empagliflozin%20on%20Free%20Fatty%20Acids%20and%20Ketone%20Bodies%20in%20Japanese%20Patients%20with%20Type%202%20Diabetes%20Mellitus:%20A%20Randomized%20Controlled%20Trial&rft.jtitle=Advances%20in%20therapy&rft.au=Nishimura,%20Rimei&rft.date=2019-10-01&rft.volume=36&rft.issue=10&rft.spage=2769&rft.epage=2782&rft.pages=2769-2782&rft.issn=0741-238X&rft.eissn=1865-8652&rft_id=info:doi/10.1007/s12325-019-01045-x&rft_dat=%3Cproquest_cross%3E2301882990%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=2301882990&rft_id=info:pmid/31444706&rfr_iscdi=true |