Studies have demonstrated that treatment of prediabetic db/db mice (from 4 to 12 weeks of age) with SIS3, a Smad3 inhibitor, significantly reduced blood glucose levels and suppressed the elevation of serum creatinine, microalbuminuria, renal fibrosis, and inflammation, thereby substantially mitigating both T2D and T2DN. Here, SMAD3 is linked to renal fibrosis.