Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor

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Background: Elevated soluble urokinase plasminogen activator receptor (suPAR) is highly associated with increased risk of diabetic complications. Dapagliflozin is a drug inhibiting the sodium-glucose co-transporter 2 in the kidney to decrease blood glucose, while also decreasing risk of kidney disease, heart failure, and death. Therefore, we have investigated suPAR as a monitor for treatment effect with dapagliflozin in diabetes. Methods: suPAR was measured in two double-blinded randomized clinical cross-over trials. The first trial investigated the effect of a single dose dapagliflozin 50 mg or placebo 12 h after intake, in individuals with type 1 diabetes and albuminuria. The second trial investigated the effect of a daily dose dapagliflozin 10 mg or placebo for 12 weeks, in individuals with type 2 diabetes and albuminuria. suPAR was measured in serum samples taken, in the acute trial, after treatment with dapagliflozin and placebo, and in the long-term trial, before and after treatment with dapagliflozin and placebo. Effect of dapagliflozin on suPAR levels were assessed using paired t-test. Results: 15 participants completed the acute trial and 35 completed the long-term trial. Mean difference in suPAR between dapagliflozin and placebo in the acute trial after 12 h was 0.70 ng/ml (95% CI: 0.66; 1.33, p = 0.49). In the long-term trial the mean difference was 0.06 ng/ml (95% CI -0.15; 0.27, p = 0.57). Conclusion: Based on our findings we conclude that suPAR is not a feasible marker to monitor the effect of treatment with dapagliflozin. Thus, a further search of suitable markers must continue.

OriginalsprogEngelsk
Artikelnummer799915
TidsskriftFrontiers in Pharmacology
Vol/bind13
ISSN1663-9812
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
T.W.H. reports having equity interest in Novo Nordisk. J.E.O is CSO, cofounder and shareholder in ViroGates, and is named inventor on patents on suPAR, owned by Copenhagen University Hospital Hvidovre, Denmark. F.P. reports having received research grants from AstraZeneca, Novo Nordisk and Novartis and lecture fees from Novartis, Eli Lilly, MSD, AstraZeneca, Sanofi, Novo Nordiskand Boehringer Ingelheim and having served as a consultant for Astra Zeneca, Bayer, Amgen, Novo Nordisk and MSD. P.R. reports giving lectures for AstraZeneca, Bayer, Novo Nordisk, Merck, and Boehringer Ingelheim; serving as a consultant for AbbVie, AstraZeneca, Bayer, Eli Lilly, Boehringer Ingelheim, Astellas, Gilead, Mundipharma, and Novo Nordisk, with all fees given to Steno Diabetes Center Copenhagen; and having equity interest in Novo Nordisk. All other authors report no competing interests. There is no external funding to declare.

Publisher Copyright:
Copyright © 2022 Rotbain Curovic, Houlind, Hansen, Eugen-Olsen, Laursen, Eickhoff, Persson and Rossing.

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