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.