Improved renal cortical oxygenation may contribute to dapagliflozin benefits
medwireNews: Randomized trial findings presented at the virtual 57th EASD Annual Meeting suggest that treatment with a high dose of the sodium-glucose cotransporter (SGLT)2 inhibitor dapagliflozin may improve renal cortical oxygenation in people with type 1 diabetes and albuminuria.
Presenting author Jens Christian Laursen (Steno Diabetes Center Copenhagen, Denmark) explained that dapagliflozin has previously been shown to improve renal outcomes and reduce overall mortality risk in patients with chronic kidney disease (CKD) with and without type 2 diabetes in the DAPA-CKD trial, but “the exact mechanisms behind these very impressive effects are still unknown.”
To investigate further, Laursen and team conducted the Astronaut phase 4 crossover trial, in which 15 individuals with type 1 diabetes and albuminuria (mean age 58 years, 33% women) were assigned to receive a single dose of dapagliflozin 50 mg and placebo in a random order, with a 2-week washout period between treatments.
The dapagliflozin dose used in this study was five times higher than the normal daily dose used in type 2 diabetes, and this was done to achieve “optimal efficacy while still being able to conduct a safe study,” noted the presenter.
He added that “dapagliflozin has a very rapid uptake within 2–4 hours,” and therefore kidney magnetic resonance imaging was carried out to assess renal oxygenation within the first 6 hours of drug administration.
The investigators found that renal cortical oxygenation improved from baseline to 6 hours following dapagliflozin treatment, but not following placebo administration, with significantly higher levels of oxygenation in the dapagliflozin group at 6 hours. There was also a trend toward improved oxygenation in the renal medulla with dapagliflozin versus placebo, but the difference did not reach statistical significance.
There were no significant differences in renal perfusion or blood flow, nor in physiologic parameters including blood pressure and heart rate, between the two treatment periods.
These findings suggest that dapagliflozin improves renal cortical oxygenation “with no indication of a changed renal oxygen supply,” said Laursen.
“Such improved oxygenation may contribute to the long-term renal beneficial effects of SGLT2 inhibitors by reducing inflammation and fibrosis,” he added.
The presenter cautioned, however, that “it remains to be determined whether the observed effects can be sustained with chronic treatment with lower doses and if they occur in type 2 diabetes as well.”
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