Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor
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 disea...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.799915/full |
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| author | Viktor Rotbain Curovic Morten B. Houlind Tine W. Hansen Jesper Eugen-Olsen Jens Christian Laursen Mie K. Eickhoff Frederik Persson Peter Rossing Peter Rossing |
| author_facet | Viktor Rotbain Curovic Morten B. Houlind Tine W. Hansen Jesper Eugen-Olsen Jens Christian Laursen Mie K. Eickhoff Frederik Persson Peter Rossing Peter Rossing |
| author_sort | Viktor Rotbain Curovic |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-12T22:15:30Z |
| format | Article |
| id | doaj.art-566f5b4cc054458fb0059e50badd6cf6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T22:15:30Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-566f5b4cc054458fb0059e50badd6cf62022-12-22T00:10:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-04-011310.3389/fphar.2022.799915799915Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator ReceptorViktor Rotbain Curovic0Morten B. Houlind1Tine W. Hansen2Jesper Eugen-Olsen3Jens Christian Laursen4Mie K. Eickhoff5Frederik Persson6Peter Rossing7Peter Rossing8Steno Diabetes Center Copenhagen, Herlev, DenmarkDepartment of Clinical Research, Hvidovre Hospital, Hvidovre, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkDepartment of Clinical Research, Hvidovre Hospital, Hvidovre, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkSteno Diabetes Center Copenhagen, Herlev, DenmarkDepartment of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkBackground: 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.799915/fulltype 1 diabetesinflammationsuPARsoluble urokinase receptorclinical trialrandomized controlled trial |
| spellingShingle | Viktor Rotbain Curovic Morten B. Houlind Tine W. Hansen Jesper Eugen-Olsen Jens Christian Laursen Mie K. Eickhoff Frederik Persson Peter Rossing Peter Rossing Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor Frontiers in Pharmacology type 1 diabetes inflammation suPAR soluble urokinase receptor clinical trial randomized controlled trial |
| title | Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor |
| title_full | Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor |
| title_fullStr | Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor |
| title_full_unstemmed | Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor |
| title_short | Acute and Long-Term Treatment With Dapagliflozin and Association With Serum Soluble Urokinase Plasminogen Activator Receptor |
| title_sort | acute and long term treatment with dapagliflozin and association with serum soluble urokinase plasminogen activator receptor |
| topic | type 1 diabetes inflammation suPAR soluble urokinase receptor clinical trial randomized controlled trial |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.799915/full |
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