AbstractAimTo 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.MethodsWe 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.ResultsThe 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).ConclusionsWe 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.