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Separate and combined effects of semaglutide and empagliflozin on kidney oxygenation and perfusion in people with type 2 diabetes: a randomised trial – published online 06/02/2023

Gullaksen graphical abstract

Søren Gullaksen, Liv Vernstrøm, Steffen S. Sørensen, Steffen Ringgaard, Christoffer Laustsen, Kristian L. Funck, Per L. Poulsen, Esben Laugesen

Diabetes mellitus is the leading cause of chronic kidney disease. Kidney hypoxia has been suggested as a unifying pathophysiological pathway in the development of chronic kidney disease in diabetes. Renoprotective effects have been documented for the sodium−glucose cotransporter 2 inhibitor empagliflozin whereas positive effects for the glucagon-like peptide-1 receptor agonist semaglutide await confirmation in dedicated kidney outcome trials. The underlying mechanisms of action of the two drugs are unclear, but it has been suggested that they may improve kidney oxygenation. In this issue, Gullaksen et al ( report that treatment with empagliflozin for 32 weeks, in contrast to previous assumptions, decreases kidney medullary oxygenation in people with type 2 diabetes. Semaglutide did not affect kidney medullary oxygenation nor was there any additional effect on oxygenation with combination therapy. The authors suggest that empagliflozin-induced medullary hypoxia may stimulate erythropoietin production, leading to kidney protection. They conclude that these findings improve our understanding of the differential kidney protective effects of empagliflozin and semaglutide.


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