Multi‐Parametric Magnetic Resonance Imaging to Assess Empagliflozin Effect on the Kidneys in People With Type 2 Diabetes Mellitus: A Pilot Clinical Trial

Aims Empagliflozin is renoprotective in Type 2 diabetes mellitus (T2DM). Our primary aim was to assess empagliflozin's effect on glomerular filtration rate and renal vascular resistance using multiparametric MRI (MpMRI). Our secondary aim was to assess the impact of empagliflozin on additional MpMRI‐derived metrics including markers of tissue oxygenation and microstructure. Materials and Methods Prospective randomised open‐label crossover clinical trial of adults with T2DM with eGFR ≥ 45 mL/min/1.73 m 2 and any degree of albuminuria (CKD KDIGO G1, 2 or GF3a, A1–A3). MpMRI was performed at baseline and 12‐weeks post‐empagliflozin or active comparator sitagliptin therapy in random order with an interval washout period. Brochner‐Mortensen corrected MRI‐derived GFR (MRI‐GFR), renal vascular resistance (RVR), renal blood flow (RBF) and markers of tissue hypoxia (R2*) and microstructure were measured. Impact of empagliflozin or sitagliptin on MpMRI and laboratory metrics were assessed with mixed‐effect linear regression. Results Twelve participants (8 male, 4 female) completed all study visits. Following empagliflozin, there were significant mean decreases in MRI‐GFR (3.03 mL/min/1.73 m 2 ) and RBF (41.24 mL/min) and increased medullary hypoxia (R2* 1.81 s −1 ) compared to sitagliptin, all p < 0.05. There were no statistically significant changes to RVR, corticomedullary microstructure, eGFR or albuminuria observed with empagliflozin. Conclusions Multiparametric MRI can non‐invasively demonstrate local renal impacts of empagliflozin beyond that of traditional markers of renal function, including decreased GFR and medullary hypoxia. Lack of RVR change may relate to lower systemic blood pressure, concurrent medication and efferent arteriolar vasodilation in T2DM.