Impact of Empagliflozin on Glomerular Hyperfiltration and Albuminuria in Youth with Type 2 Diabetes: Post-Hoc Analysis of DINAMO

Background: Hyperfiltration, common in youth with type 2 diabetes (T2D), may increase risk for early diabetic kidney disease (DKD). The DINAMO and DINAMO MONO trials showed that versus placebo, empagliflozin improved glycemic control in youth with T2D. This post-hoc analysis evaluated empagliflozin versus placebo on selected parameters in participants from both trials according to their baseline hyperfiltration/normofiltration status. Methods: We calculated eGFR using the Zappitelli equation (combined serum creatinine and cystatin C), with hyperfiltration defined as 2 standard deviations above average for healthy youth per National Health and Nutrition Examination Survey (NHANES; >126.8 mL/min per 1.73 m 2 ). After randomization, 116 participants received empagliflozin (10 out of25 mg) or placebo. We compared responses to therapy for estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) at Week 26 by baseline hyperfiltration and normofiltration (≤126.8 mL/min per 1.73 m 2 ), with empagliflozin groups pooled. Results: Empagliflozin treatment led to more significant reductions in eGFR among participants with baseline hyperfiltration compared with normofiltration ( P interaction = 0.01). At Week 26, eGFR decreased significantly with empagliflozin versus placebo in those with hyperfiltration (adjusted mean difference [95% confidence interval {CI}], -11.67 mL/min per 1.73 m 2 [-19.90, -3.43]; P = 0.006); 15% of those with hyperfiltration on empagliflozin shifted to normofiltration at Week 26 versus 6% for placebo. At Week 26, the geometric mean ratio of UACR was 55% lower with empagliflozin versus placebo in participants with UACR ≥30 mg/g at baseline (0.45 [0.22-0.93]; P = 0.03). In the normofiltration subgroup, eGFR and UACR changes over time were similar between treatment groups. Conclusions: Empagliflozin was associated with attenuated hyperfiltration and albuminuria in youth with T2D. Future longitudinal evaluations can assess potential long-term benefits of treatment.