Among gliptins, linagliptin is unique, because decreased glomerular filtration rate does not require dose reduction. Linagliptin was originally developed to lower blood glucose by inhibiting dipeptidyl peptidase-4 (DPP-4). However, DPP-4 has numerous additional substrates, and thus gliptins possess a vast range of additional off-target effects. Shi et al. report that linagliptin directly targets interaction of DPP-4 with integrin β1, preventing endothelial-mesenchymal transition and ultimately renal fibrosis, providing additional rationale for use of linagliptin in diabetic nephropathy.