Effects of 6weeks of treatment with dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo‐controlled, exploratory study
AimTo explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure.Materials and MethodsPatients with type 2 diabetes on metformin treatment were randomized to double‐blind, 6‐week placebo or dapagliflozin 10 mg daily treatme...
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| Veröffentlicht in: | Diabetes, obesity & metabolism obesity & metabolism, 2021-07, Vol.23 (7), p.1505-1517 |
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| creator | Oldgren, Jonas Laurila, Sanna Åkerblom, Axel Aino Latva‐Rasku Rebelos, Eleni Isackson, Henrik Saarenhovi, Maria Eriksson, Olof Heurling, Kerstin Johansson, Edvin Wilderäng, Ulrica Karlsson, Cecilia Esterline, Russell Ferrannini, Ele Oscarsson, Jan Nuutila, Pirjo |
| description | AimTo explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure.Materials and MethodsPatients with type 2 diabetes on metformin treatment were randomized to double‐blind, 6‐week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [11C]‐acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18F]‐6‐thia‐heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals.ResultsEvaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m2 and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (−0.095 [−0.145, −0.043] J/g/min) and LV oxygen consumption were significantly reduced (−0.30 [−0.49, −0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was −3.19 (−6.32, −0.07) mL/m2 (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (−3.92% [−7.57%, −0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] μmol/g/min; p = .018), while cardiac uptake was unchanged.ConclusionsThis exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin. |
| doi_str_mv | 10.1111/dom.14363 |
| format | Article |
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Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [11C]‐acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18F]‐6‐thia‐heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals.ResultsEvaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m2 and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (−0.095 [−0.145, −0.043] J/g/min) and LV oxygen consumption were significantly reduced (−0.30 [−0.49, −0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was −3.19 (−6.32, −0.07) mL/m2 (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (−3.92% [−7.57%, −0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] μmol/g/min; p = .018), while cardiac uptake was unchanged.ConclusionsThis exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.</description><identifier>ISSN: 1462-8902</identifier><identifier>EISSN: 1463-1326</identifier><identifier>DOI: 10.1111/dom.14363</identifier><language>eng</language><publisher>Oxford: Wiley Subscription Services, Inc</publisher><subject>Acetic acid ; Antidiabetics ; Body mass index ; Body weight ; Congestive heart failure ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Efficiency ; Fatty acids ; Fatty liver ; Glucose transporter ; Metabolism ; Metformin ; Oxygen consumption ; Perfusion ; Placebos ; Positron emission tomography ; Statistical analysis ; Structure-function relationships ; Ventricle</subject><ispartof>Diabetes, obesity & metabolism, 2021-07, Vol.23 (7), p.1505-1517</ispartof><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></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></links><search><creatorcontrib>Oldgren, Jonas</creatorcontrib><creatorcontrib>Laurila, Sanna</creatorcontrib><creatorcontrib>Åkerblom, Axel</creatorcontrib><creatorcontrib>Aino Latva‐Rasku</creatorcontrib><creatorcontrib>Rebelos, Eleni</creatorcontrib><creatorcontrib>Isackson, Henrik</creatorcontrib><creatorcontrib>Saarenhovi, Maria</creatorcontrib><creatorcontrib>Eriksson, Olof</creatorcontrib><creatorcontrib>Heurling, Kerstin</creatorcontrib><creatorcontrib>Johansson, Edvin</creatorcontrib><creatorcontrib>Wilderäng, Ulrica</creatorcontrib><creatorcontrib>Karlsson, Cecilia</creatorcontrib><creatorcontrib>Esterline, Russell</creatorcontrib><creatorcontrib>Ferrannini, Ele</creatorcontrib><creatorcontrib>Oscarsson, Jan</creatorcontrib><creatorcontrib>Nuutila, Pirjo</creatorcontrib><title>Effects of 6weeks of treatment with dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo‐controlled, exploratory study</title><title>Diabetes, obesity & metabolism</title><description>AimTo explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure.Materials and MethodsPatients with type 2 diabetes on metformin treatment were randomized to double‐blind, 6‐week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [11C]‐acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18F]‐6‐thia‐heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals.ResultsEvaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m2 and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (−0.095 [−0.145, −0.043] J/g/min) and LV oxygen consumption were significantly reduced (−0.30 [−0.49, −0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was −3.19 (−6.32, −0.07) mL/m2 (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (−3.92% [−7.57%, −0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] μmol/g/min; p = .018), while cardiac uptake was unchanged.ConclusionsThis exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.</description><subject>Acetic acid</subject><subject>Antidiabetics</subject><subject>Body mass index</subject><subject>Body weight</subject><subject>Congestive heart failure</subject><subject>Diabetes</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Efficiency</subject><subject>Fatty acids</subject><subject>Fatty liver</subject><subject>Glucose transporter</subject><subject>Metabolism</subject><subject>Metformin</subject><subject>Oxygen consumption</subject><subject>Perfusion</subject><subject>Placebos</subject><subject>Positron emission tomography</subject><subject>Statistical analysis</subject><subject>Structure-function relationships</subject><subject>Ventricle</subject><issn>1462-8902</issn><issn>1463-1326</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><recordid>eNqNj01Ow0AMhSMEEuVnwQ0ssU1LJgkhZYdQEQdgX01mnHbKZBxmHJV0xRE4I1yEaeEAeGO_Zz99cpJciWwmYt1o6maiLKriKJmIsiqmosir48OcT-t5lp8mZyFssiwri_puknwv2hYVB6AWqi3i62Fij5I7dAxbw2vQspcra1pLO-NSkBBIm6H7-vhc2UFRQFAUBXvpQk-e0UeVg3Fr0xgmnwI56EZS0msjLbSDU2yiJ52GDlk2ZE3oYgB6ySZywy-Yxx4hhxhqkDHcwwNERvzR7FCn0FupsNmjFTn2ZO3exffekpeRO0LgQY8XyUkrbcDLv36eXD8tXh6fp72ntwEDLzc0eBdXy_y2FGJeV2Vd_O_qB5UKf5c</recordid><startdate>20210701</startdate><enddate>20210701</enddate><creator>Oldgren, Jonas</creator><creator>Laurila, Sanna</creator><creator>Åkerblom, Axel</creator><creator>Aino Latva‐Rasku</creator><creator>Rebelos, Eleni</creator><creator>Isackson, Henrik</creator><creator>Saarenhovi, Maria</creator><creator>Eriksson, Olof</creator><creator>Heurling, Kerstin</creator><creator>Johansson, Edvin</creator><creator>Wilderäng, Ulrica</creator><creator>Karlsson, Cecilia</creator><creator>Esterline, Russell</creator><creator>Ferrannini, Ele</creator><creator>Oscarsson, Jan</creator><creator>Nuutila, Pirjo</creator><general>Wiley Subscription Services, Inc</general><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>K9.</scope></search><sort><creationdate>20210701</creationdate><title>Effects of 6weeks of treatment with dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo‐controlled, exploratory study</title><author>Oldgren, Jonas ; Laurila, Sanna ; Åkerblom, Axel ; Aino Latva‐Rasku ; Rebelos, Eleni ; Isackson, Henrik ; Saarenhovi, Maria ; Eriksson, Olof ; Heurling, Kerstin ; Johansson, Edvin ; Wilderäng, Ulrica ; Karlsson, Cecilia ; Esterline, Russell ; Ferrannini, Ele ; Oscarsson, Jan ; Nuutila, Pirjo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-proquest_journals_25411986483</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Acetic acid</topic><topic>Antidiabetics</topic><topic>Body mass index</topic><topic>Body weight</topic><topic>Congestive heart failure</topic><topic>Diabetes</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Efficiency</topic><topic>Fatty acids</topic><topic>Fatty liver</topic><topic>Glucose transporter</topic><topic>Metabolism</topic><topic>Metformin</topic><topic>Oxygen consumption</topic><topic>Perfusion</topic><topic>Placebos</topic><topic>Positron emission tomography</topic><topic>Statistical analysis</topic><topic>Structure-function relationships</topic><topic>Ventricle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Oldgren, Jonas</creatorcontrib><creatorcontrib>Laurila, Sanna</creatorcontrib><creatorcontrib>Åkerblom, Axel</creatorcontrib><creatorcontrib>Aino Latva‐Rasku</creatorcontrib><creatorcontrib>Rebelos, Eleni</creatorcontrib><creatorcontrib>Isackson, Henrik</creatorcontrib><creatorcontrib>Saarenhovi, Maria</creatorcontrib><creatorcontrib>Eriksson, Olof</creatorcontrib><creatorcontrib>Heurling, Kerstin</creatorcontrib><creatorcontrib>Johansson, Edvin</creatorcontrib><creatorcontrib>Wilderäng, Ulrica</creatorcontrib><creatorcontrib>Karlsson, Cecilia</creatorcontrib><creatorcontrib>Esterline, Russell</creatorcontrib><creatorcontrib>Ferrannini, Ele</creatorcontrib><creatorcontrib>Oscarsson, Jan</creatorcontrib><creatorcontrib>Nuutila, Pirjo</creatorcontrib><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><jtitle>Diabetes, obesity & metabolism</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Oldgren, Jonas</au><au>Laurila, Sanna</au><au>Åkerblom, Axel</au><au>Aino Latva‐Rasku</au><au>Rebelos, Eleni</au><au>Isackson, Henrik</au><au>Saarenhovi, Maria</au><au>Eriksson, Olof</au><au>Heurling, Kerstin</au><au>Johansson, Edvin</au><au>Wilderäng, Ulrica</au><au>Karlsson, Cecilia</au><au>Esterline, Russell</au><au>Ferrannini, Ele</au><au>Oscarsson, Jan</au><au>Nuutila, Pirjo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of 6weeks of treatment with dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo‐controlled, exploratory study</atitle><jtitle>Diabetes, obesity & metabolism</jtitle><date>2021-07-01</date><risdate>2021</risdate><volume>23</volume><issue>7</issue><spage>1505</spage><epage>1517</epage><pages>1505-1517</pages><issn>1462-8902</issn><eissn>1463-1326</eissn><abstract>AimTo explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure.Materials and MethodsPatients with type 2 diabetes on metformin treatment were randomized to double‐blind, 6‐week placebo or dapagliflozin 10 mg daily treatment. Investigations included cardiac function and structure with myocardial resonance imaging; cardiac oxygen consumption, perfusion and efficiency with [11C]‐acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18F]‐6‐thia‐heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals.ResultsEvaluable patients (placebo: n = 24, dapagliflozin: n = 25; 53% males) had a mean age of 64.4 years, a body mass index of 30.2 kg/m2 and an HbA1c of 6.7%. Body weight and HbA1c were significantly decreased by dapagliflozin versus placebo. Dapagliflozin had no effect on myocardial efficiency, but external left ventricular (LV) work (−0.095 [−0.145, −0.043] J/g/min) and LV oxygen consumption were significantly reduced (−0.30 [−0.49, −0.12] J/g/min) by dapagliflozin, although the changes were not statistically significant versus changes in the placebo group. Change in left atrial maximal volume with dapagliflozin versus placebo was −3.19 (−6.32, −0.07) mL/m2 (p = .056). Peak global radial strain decreased with dapagliflozin versus placebo (−3.92% [−7.57%, −0.28%]; p = .035), while peak global longitudinal and circumferential strains were unchanged. Hepatic fatty acid uptake was increased by dapagliflozin versus placebo (0.024 [0.004, 0.044] μmol/g/min; p = .018), while cardiac uptake was unchanged.ConclusionsThis exploratory study indicates reduced heart work but limited effects on myocardial function, efficiency and cardiac fatty acid uptake, while hepatic fatty acid uptake increased, after 6 weeks of treatment with dapagliflozin.</abstract><cop>Oxford</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1111/dom.14363</doi></addata></record> |
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| subjects | Acetic acid Antidiabetics Body mass index Body weight Congestive heart failure Diabetes Diabetes mellitus (non-insulin dependent) Efficiency Fatty acids Fatty liver Glucose transporter Metabolism Metformin Oxygen consumption Perfusion Placebos Positron emission tomography Statistical analysis Structure-function relationships Ventricle |
| title | Effects of 6weeks of treatment with dapagliflozin, a sodium‐glucose co‐transporter‐2 inhibitor, on myocardial function and metabolism in patients with type 2 diabetes: A randomized, placebo‐controlled, exploratory study |
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