We investigated for the first time the effect of combination therapy of renin–angiotensin system inhibition (RASi) and sodium–glucose co-transporter-2 inhibitors (SGLT2is) on endotrophin (ETP), a pro-fibrotic signaling molecule reflecting collagen type VI formation, measured in the plasma of persons with type 2 diabetes (T2D). Here, REN is linked to type 2 diabetes mellitus.