Addition of silymarin to renin-angiotensin system blockers in normotensive patients with type 2 diabetes mellitus and proteinuria: a prospective randomized trial.

Background: In the last decade, despite constant investigation, no current single treatment has been able to decrease the incidence of diabetic nephropathy and to significantly reduce progression of diabetic CKD.

Methods: Patients with type 2 diabetes mellitus and proteinuria (>0.5 g/day) after a screening and treatment optimization phase were randomly assigned to receive silymarin or placebo. The primary outcome was a composite outcome: mortality, decline of eGFR > 50% and renal replacement therapy. Secondary outcomes were a composite renal outcome (defined as a decline of eGFR ≥ 50% or ESRD) and also to test the effect of silymarin on the change in eGFR and proteinuria. We also assessed the adverse effects (hospitalizations, headache or gastrointestinal symptoms) during the study.

Results: One hundred and two patients were included in the study. There were no significant differences between the two study groups regarding the primary and renal outcomes (HR 0.62, 95% CI 0.3-1.2, p = 0.15; HR 0.56, 95% CI 0.26-1.24, p = 0.16, respectively). At study end, eGFR declined significantly in both arms (p < 0.001), irrespective of the treatment group allocation, and there were no significant changes in proteinuria. There was a significant difference in hospitalizations rates between the two study groups (0.61, 95% CI 0.44-0.85).

Conclusions: Silymarin did not show a significant reduction in the primary and secondary outcomes. Importantly, silymarin treatment was associated with a significant reduction in the hospitalization rate.