The role of empagliflozin-induced metabolic changes for cardiac function in patients with type 2 diabetes. A randomized cross-over magnetic resonance imaging study with insulin as comparator

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Background: Metabolic effects of empagliflozin treatment include lowered glucose and insulin concentrations, elevated free fatty acids and ketone bodies and have been suggested to contribute to the cardiovascular benefits of empagliflozin treatment, possibly through an improved cardiac function. We aimed to evaluate the influence of these metabolic changes on cardiac function in patients with T2D. Methods: In a randomized cross-over design, the SGLT2 inhibitor empagliflozin (E) was compared with insulin (I) treatment titrated to the same level of glycemic control in 17 patients with type 2 diabetes, BMI of > 28 kg/m2, C-peptide > 500 pM. Treatments lasted 5 weeks and were preceded by 3-week washouts (WO). At the end of treatments and washouts, cardiac diastolic function was determined with magnetic resonance imaging from left ventricle early peak-filling rate and left atrial passive emptying fraction (primary and key secondary endpoints); systolic function from left ventricle ejection fraction (secondary endpoint). Coupling between cardiac function and fatty acid concentrations, was studied on a separate day with a second scan after reduction of plasma fatty acids with acipimox. Data are Mean ± standard error. Between treatment difference (ΔT: E–I) and treatments effects (ΔE: E-WO or ΔI: I -WO) were evaluated using Students’ t-test or Wilcoxon signed rank test as appropriate. Results: Glucose concentrations were similar, fatty acids, ketone bodies and lipid oxidation increased while insulin concentrations decreased on empagliflozin compared with insulin treatment. Cardiac diastolic and systolic function were unchanged by either treatment. Acipimox decreased fatty acids with 35% at all visits, and this led to reduced cardiac diastolic (ΔT: −51 ± 22 ml/s (p < 0.05); ΔE: −33 ± 26 ml/s (ns); ΔI: 37 ± 26 (ns, p < 0.05 vs ΔE)) and systolic function (ΔT: -3 ± 1% (p < 0.05); ΔE: −3 ± 1% (p < 0.05): ΔI: 1 ± 2 (ns, ns vs ΔE)) under chronotropic stress during empagliflozin compared to insulin treatment. Conclusions: Despite significant metabolic differences, cardiac function did not differ on empagliflozin compared with insulin treatment. Impaired cardiac function during acipimox treatment, could suggest greater cardiac reliance on lipid metabolism for proper function during empagliflozin treatment in patients with type 2 diabetes. Trial registration: EudraCT 2017-002101-35, August 2017.

TidsskriftCardiovascular Diabetology
Udgave nummer1
Sider (fra-til)1-13
StatusUdgivet - 2024

Bibliografisk note

Funding Information:
J.P.G. has been a paid Consultant for Novo Nordisk A/S. J.J.H.: has participated in advisory panels for Novo Nordisk and is a board member of Antag Therapeutics and Bainan Biotech. S.M.: has participated on advisory boards for AstraZeneca, Boehringer Ingelheim, Eli Lilly, Intarcia Therapeutics, MSD, Novartis, Novo Nordisk and Sanofi and speaker’s bureau for AstraZeneca, Boehringer Ingelheim, MSD, Novo Nordisk and Sanofi. S.M. has also received research grants from Novo Nordisk and Boehringer Ingelheim. N.B.J.: has participated on advisory panels for Novo Nordisk Denmark and speaker’s bureau for Novo Nordisk Denmark A/S and Boehringer Ingelheim Denmark, has received research grants from Boehringer Ingelheim, and has recently taken a position with Novo Nordisk A/S, Søborg, Denmark.

Publisher Copyright:
© 2024, The Author(s).

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