AIM: To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. MATERIALS AND METHODS: Patients 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 [11 C]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18 F]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. RESULTS:Evaluable 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. CONCLUSIONS: This 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.
RCT Entities:
AIM: To explore the early effects of dapagliflozin on myocardial function and metabolism in patients with type 2 diabetes without heart failure. MATERIALS AND METHODS:Patients 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 [11 C]-acetate positron emission tomography (PET); and cardiac and hepatic fatty acid uptake with [18 F]-6-thia-heptadecanoic acid PET, analysed by ANCOVA as least square means with 95% confidence intervals. RESULTS: Evaluable 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. CONCLUSIONS: This 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.
Authors: Kristina Wallenius; Tobias Kroon; Therese Hagstedt; Lars Löfgren; Maria Sörhede-Winzell; Jeremie Boucher; Daniel Lindén; Nicholas D Oakes Journal: J Lipid Res Date: 2022-02-02 Impact factor: 5.922
Authors: Caitlin Fern Wee; Yao Hao Teo; Yao Neng Teo; Nicholas Lx Syn; Ray Meng See; Shariel Leong; Alicia Swee Yan Yip; Zhi Xian Ong; Chi-Hang Lee; Mark Yan-Yee Chan; Kian-Keong Poh; Ching-Ching Ong; Lynette Ls Teo; Devinder Singh; Benjamin Yq Tan; Leonard Ll Yeo; William Kf Kong; Tiong-Cheng Yeo; Raymond Cc Wong; Ping Chai; Ching-Hui Sia Journal: J Cardiovasc Imaging Date: 2022-07
Authors: Esben Søndergaard; Esben S Lauritzen; Katrine M Lauritsen; Axel Åkerblom; Pirjo Nuutila; Jonas Oldgren; Lars C Gormsen Journal: Metabol Open Date: 2022-08-23
Authors: Huitzilihuitl Saucedo-Orozco; Suzanne N Voorrips; Salva R Yurista; Rudolf A de Boer; B Daan Westenbrink Journal: J Lipid Atheroscler Date: 2022-01-13