Overall and inter-individual effect of four different drug classes on soluble urokinase plasminogen activator receptor in type 1 and type 2 diabetes
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Overall and inter-individual effect of four different drug classes on soluble urokinase plasminogen activator receptor in type 1 and type 2 diabetes. / Rotbain Curovic, Viktor; Houlind, Morten B.; Kroonen, Marjolein Y.A.M.; Jongs, Niels; Zobel, Emilie H.; Hansen, Tine W.; Tavenier, Juliette; Eugen-Olsen, Jesper; Laverman, Gozewijn D.; Kooy, Adriaan; Persson, Frederik; Rossing, Peter; Heerspink, Hiddo J.L.
In: Diabetes, Obesity and Metabolism, Vol. 25, No. 11, 2023, p. 3152-3160.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Overall and inter-individual effect of four different drug classes on soluble urokinase plasminogen activator receptor in type 1 and type 2 diabetes
AU - Rotbain Curovic, Viktor
AU - Houlind, Morten B.
AU - Kroonen, Marjolein Y.A.M.
AU - Jongs, Niels
AU - Zobel, Emilie H.
AU - Hansen, Tine W.
AU - Tavenier, Juliette
AU - Eugen-Olsen, Jesper
AU - Laverman, Gozewijn D.
AU - Kooy, Adriaan
AU - Persson, Frederik
AU - Rossing, Peter
AU - Heerspink, Hiddo J.L.
N1 - Publisher Copyright: © 2023 John Wiley & Sons Ltd.
PY - 2023
Y1 - 2023
N2 - Aim: To evaluate the effect of four different drug classes on soluble urokinase plasminogen activator receptor (suPAR), a biomarker active in multiple inflammatory processes and a risk factor for complications, in people with type 1 and type 2 diabetes. Methods: We conducted post hoc analyses of a randomized, open-label, crossover trial including 26 adults with type 1 and 40 with type 2 diabetes with urinary albumin-creatinine ratio ≥30 and ≤500 mg/g assigned to 4-week treatments with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg and baricitinib 2 mg, separated by 4-week washouts. Plasma suPAR was measured before and after each treatment. SuPAR change after each treatment was calculated and, for each individual, the best suPAR-reducing drug was identified. Subsequently, the effect of the best individual drug was compared against the mean of the other three drugs. Repeated-measures linear mixed-effects models were employed. Results: The baseline median (interquartile range) plasma suPAR was 3.5 (2.9, 4.3) ng/mL. No overall effect on suPAR levels was observed for any one drug. The individual best-performing drug varied, with baricitinib being selected for 20 participants (30%), followed by empagliflozin for 19 (29%), linagliptin for 16 (24%) and telmisartan for 11 (17%). The individual best-performing drug reduced suPAR by 13.3% (95% confidence interval [CI] 3.7, 22.8; P = 0.007). The difference in suPAR response between the individual best-performing drug and the other three was −19.7% (95% CI −23.1, −16.3; P < 0.001). Conclusions: We demonstrated no overall effect of 4-week treatment with telmisartan, empagliflozin, linagliptin or baricitinib on suPAR. However, individualization of treatment might significantly reduce suPAR levels.
AB - Aim: To evaluate the effect of four different drug classes on soluble urokinase plasminogen activator receptor (suPAR), a biomarker active in multiple inflammatory processes and a risk factor for complications, in people with type 1 and type 2 diabetes. Methods: We conducted post hoc analyses of a randomized, open-label, crossover trial including 26 adults with type 1 and 40 with type 2 diabetes with urinary albumin-creatinine ratio ≥30 and ≤500 mg/g assigned to 4-week treatments with telmisartan 80 mg, empagliflozin 10 mg, linagliptin 5 mg and baricitinib 2 mg, separated by 4-week washouts. Plasma suPAR was measured before and after each treatment. SuPAR change after each treatment was calculated and, for each individual, the best suPAR-reducing drug was identified. Subsequently, the effect of the best individual drug was compared against the mean of the other three drugs. Repeated-measures linear mixed-effects models were employed. Results: The baseline median (interquartile range) plasma suPAR was 3.5 (2.9, 4.3) ng/mL. No overall effect on suPAR levels was observed for any one drug. The individual best-performing drug varied, with baricitinib being selected for 20 participants (30%), followed by empagliflozin for 19 (29%), linagliptin for 16 (24%) and telmisartan for 11 (17%). The individual best-performing drug reduced suPAR by 13.3% (95% confidence interval [CI] 3.7, 22.8; P = 0.007). The difference in suPAR response between the individual best-performing drug and the other three was −19.7% (95% CI −23.1, −16.3; P < 0.001). Conclusions: We demonstrated no overall effect of 4-week treatment with telmisartan, empagliflozin, linagliptin or baricitinib on suPAR. However, individualization of treatment might significantly reduce suPAR levels.
KW - albuminuria
KW - angiotensin receptor blocker
KW - baricitinib
KW - chronic kidney disease
KW - dipeptidyl peptidase-4 inhibitor
KW - inflammation
KW - JAK–STAT inhibitor
KW - personalized medicine
KW - SGLT2 inhibitor
U2 - 10.1111/dom.15209
DO - 10.1111/dom.15209
M3 - Journal article
C2 - 37417375
AN - SCOPUS:85164483261
VL - 25
SP - 3152
EP - 3160
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 11
ER -
ID: 365709882