Overall and inter-individual effect of four different drug classes on soluble urokinase plasminogen activator receptor in type 1 and type 2 diabetes.

Autor: Rotbain Curovic V; Steno Diabetes Center Copenhagen, Herlev, Denmark., Houlind MB; Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark.; University of Copenhagen, Copenhagen, Denmark., Kroonen MYAM; University Medical Center Groningen, Groningen, Netherlands., Jongs N; University Medical Center Groningen, Groningen, Netherlands., Zobel EH; Steno Diabetes Center Copenhagen, Herlev, Denmark., Hansen TW; Steno Diabetes Center Copenhagen, Herlev, Denmark., Tavenier J; Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark., Eugen-Olsen J; Copenhagen University Hospital-Amager and Hvidovre, Hvidovre, Denmark., Laverman GD; ZiekenhuisGroep Twente, Almelo, Netherlands., Kooy A; University Medical Center Groningen, Groningen, Netherlands.; Bethesda Diabetes Research Center, Hoogeveen, Netherlands., Persson F; Steno Diabetes Center Copenhagen, Herlev, Denmark., Rossing P; Steno Diabetes Center Copenhagen, Herlev, Denmark.; University of Copenhagen, Copenhagen, Denmark., Heerspink HJL; University Medical Center Groningen, Groningen, Netherlands.
Jazyk: angličtina
Zdroj: Diabetes, obesity & metabolism [Diabetes Obes Metab] 2023 Nov; Vol. 25 (11), pp. 3152-3160. Date of Electronic Publication: 2023 Jul 07.
DOI: 10.1111/dom.15209
Abstrakt: 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.
(© 2023 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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