FP485EFFECTS OF ERTUGLIFLOZIN TREATMENT OVER 2 YEARS ON MEASURES OF RENAL FUNCTION

INTRODUCTION: Two RCTs evaluating ertugliflozin 5 mg (E5, n=652), 15 mg (E15, n=640) vs non-ertugliflozin (NE, glimepiride or placebo, n=644) in patients with type 2 diabetes (T2D) were pooled to evaluate effects of ertugliflozin on eGFR and albuminuria. METHODS: Change over time in eGFR (MDRD) and UACR (UACR, geometric mean of % change from baseline) were analysed by mixed model repeated measures in the overall population and by baseline UACR category (UACR <30 mg/g or ≥30 mg/g). Transition in albuminuria category (UACR <30 or ≥30 mg/g) was analysed by calculating the transition from baseline to week 104. The rate of change in eGFR (eGFR slope) per week, was analyzed by random coefficient models. The model included eGFR value as response variable with treatment group, time in weeks, treatment by time interaction, and baseline eGFR as fixed effects. Two study periods (0-6 and 6-104 week) were modeled separately. RESULTS: Baseline characteristics were balanced among the treatment groups. Overall, mean baseline eGFR was 88.2 ml/min/1.73m² and geometric mean baseline UACR was 11.6 mg/g. In patients with baseline UACR < 30 mg/g (n=1521) mean values for UACR over time were similar between groups. In patients with baseline UACR ≥30 mg/g (n=415) the week 104 ΔUACR [95% CI] compared to NE was -29.0% ([-47.0, -4.5]; p=0.02) for E5 and -32.7% ([95%CI -50.4, -8.6]; p=0.01) for E15. In patients with baseline UACR <30 mg/g the proportion of patients that transitioned to the UACR ≥30 mg/g category at week 104 were 11.5, 10.6 and 7.4%, respectively for the NE, E5 and E15 groups. The difference vs. NE were non-significant. Of the patients with baseline UACR ≥30 mg/g the proportion of patients that transitioned to the UACR <30 mg/g category at week 104 were 31.8, 37.3 and 44.1%, respectively for the NE, E5 and E15 groups. The difference vs. NE were non-significant. At week 6, changes from baseline in eGFR were: -2.3, -2.7 and -0.7 ml/min/1.73m², for the E5, E15 and NE groups, respectively. From week 6, mean eGFR with ertugliflozin increased over time, while it decreased in the NE group. The week 104 ΔeGFR [95% CI] from baseline compared to NE was 1.81 ([0.13, 3.49]; p=0.04) and 2.10 ml/min/1.73m² ([0.42, 3.78]; p=0.01) for E5 and E15, respectively. For the 0 to 6-week treatment period the mean (95% CI) weekly change from baseline in the eGFR slope were -0.10 (-0.32, 0.13), -0.38 (-0.60, -0.15), and -0.45 (-0.68, -0.21) respectively for the NE, E5 and E15 groups. The mean weekly NE-corrected differences were -0.29 [(-0.61, 0.04) p=0.08] and -0.35 [(-0.68, -0.02) p=0.04] for the E5 and E15 groups. For the 6 to 104-week treatment period the mean (95% CI) weekly change from baseline in eGFR slope were -0.01 (-0.02, -0.004), 0.02 (0.01, 0.03), 0.03 (0.02, 0.04) ml/min/1.73m² respectively for the NE, E5 and E15 groups, which corresponds to a slope over the 98 week period of -0.98, 1.96 and 2.94, respectively for the NE, E5 and E15 groups. Results were similar by baseline UACR category. CONCLUSIONS: Ertugliflozin acutely (first 6 weeks) reduced eGFR possibly based on known hemodynamic effects. At week 104, eGFR values were higher with ertugliflozin than control. The significant decreases in UACR in patients with baseline elevated albuminuria along with significant differences in eGFR are suggestive of renal function preservation with ertugliflozin treatment.

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