EASD 2020 Highlights

Conference summaries


T2D & CVD

Empagliflozin reduces myocardial glucose uptake in persons with type 2 diabetes: a randomised double-blind, placebo-controlled crossover study

Presented by:

Katrine M. Lauritsen, MD


  • This randomised trial investigated the effects of empagliflozin on cardiac uptake of free fatty acids and glucose.
  • Empagliflozin had no significant effects on myocardial uptake of free fatty acids.
  • Empagliflozin led to less glucose uptake in the heart, from about 2% of total cardiac energy expenditure to about 1%.

What do we already know about this topic?

  • It has been hypothesised that under conditions of mild, persistent hyperketonaemia, such as those present during treatment with SGLT2 inhibitors, β-hydroxybutyrate is freely taken up by the heart (among other organs) and preferentially oxidized over fatty acids.1
  • This selection improves the transduction of oxygen consumption into work efficiency at the mitochondrial level.1
  • In addition, the haemoconcentration that typically follows SGLT2 inhibition enhances oxygen release to tissues, thus establishing synergy with the metabolic substrate shift.1
  • These mechanisms might cooperate with other SGLT2 inhibition-induced changes (chiefly, enhanced diuresis and reduced blood pressure) to achieve the degree of cardioprotection observed in clinical trials.1

How was this study conducted?

  • The EMPA-PET trial examined the possibility that empagliflozin decreases cardiac uptake of free fatty acids and glucose as a consequence of an increase in ketone body oxidation.
  • Mean age of participants was 62 years with mean BMI of 31.5 kg/m2, HbA1c of 56.7 mmol/mol and all were on metformin.
  • Patients were randomised to empagliflozin or placebo for 4 weeks, and following a 1-week wash-out period crossed over treatments for another 4-week period.
  • PET/CT multitracer analyses were carried out using 11C-acetate, 11C-palmitate and 18F-FDG.

What does this study add?

  • Compared to placebo, empagliflozin increased the levels of both free fatty acids and ketone bodies.
  • Empagliflozin did not affect myocardial free fatty acid uptake compared to placebo, although it did reduce myocardial glucose uptake.
  • Although glucose uptake was reduced, it was responsible for only about 2% of the total energy expenditure of the heart compared to 48% for free fatty acids, which was reduced to about 1% during treatment with empagliflozin.
  • Empagliflozin did not significantly affect myocardial oxygen consumption or myocardial external efficiency.

Perspectives

How does this study impact clinical practice?

  • Empagliflozin did not significantly alter myocardial uptake of free fatty acids, although this effect could be different in patients with cardiac disease.
  • Empagliflozin led to a cardiac substrate shift away from glucose.
  • The effect of empagliflozin on cardiac oxygen demand needs to be further investigated.


References

References


  1. Ferrannini E, Mark M, Mayoux E. CV Protection in the EMPA-REG OUTCOME Trial: A “Thrifty Substrate” hypothesis. Diabetes Care. 2016 Jul;39(7):1108-14.

 

Related content

  • Abdurrachim D, Teo XQ, Woo CC, et al. Empagliflozin reduces myocardial ketone utilization while preserving glucose utilization in diabetic hypertensive heart disease: A hyperpolarized 13 C magnetic resonance spectroscopy study. Diabetes Obes Metab. 2019 Feb;21(2):357-65.

 



Acknowledgements

This is a highlights summary of an oral session given at the EASD 2020 Virtual Meeting and presented by:

Katrine M. Lauritsen, MD
Dept. of Internal Medicine and Endocrinology, Aarhus University Hospital; Danish Diabetes Academy, Odense University Hospital; Steno Diabetes Center Aarhus, Denmark

The presenting authors of the original session had no part in the creation of this conference highlights summary. 

The content is produced by Infomedica. The summary text was drafted by Patrick Moore, PhD, and reviewed by Marco Gallo, MD, an independent external expert, and approved by Florian Toti, MD, the scientific editor of the program.


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Presented by: Patrick M. Catalano, MD
Expert commentary by Elizabeth O. Buschur, MD

DIABETES & HF

Empagliflozin for the treatment of chronic heart failure and a reduced ejection fraction in patients with and without diabetes: new results of the EMPEROR-Reduced trial

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Expert commentary by Prof. Francesco Giorgino

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