This post-hoc CREDENCE analysis showed that SGLT2 inhibition remains safe and effective when eGFR declines below 20 mL/min, supporting continuation of therapy in patients with severely reduced kidney function rather than discontinuation at an arbitrary eGFR threshold.
Clinical practice guidelines recommend initiation of SGLT2 inhibitors when eGFR ≥20ml/min/1.73m2. While continuing SGLT2 inhibitors when eGFR falls <20ml/min/1.73m2 is recommended, data on the efficacy and safety of SGLT2i in this setting are limited.
In this post-hoc analysis of the CREDENCE trial, we used time-updated Cox proportional hazards models to assess the association between deterioration in eGFR to <20 ml/min/1.73m2, efficacy and safety outcomes, and treatment with canagliflozin.
Among 4,401 randomized participants, 443 (10.1%) experienced eGFR deterioration to <20 ml/min/1.73m2 at least once in follow up. These participants experienced a higher risk of the primary composite outcome (HR 10.68; 95%CI: 8.50-13.41; P<0.001). Canagliflozin compared with placebo was associated with a lower risk of the primary outcome among participants who did (HR 0.87; 95%CI: 0.61-1.25) and did not (HR 0.69; 95%CI: 0.57-0.84) experience deterioration of eGFR to <20 ml/min/1.73m2 (PInteraction=0.18). While the incidence of adverse outcomes were higher among participants whose eGFR fell <20 ml/min/1.73m2, event rates remained similar between treatment groups irrespective of eGFR decline <20 ml/min/1.73m2.
In patients with type 2 diabetes and CKD whose eGFR fell <20ml/min/1.73m2, continuation of canagliflozin was associated with persistent benefit for kidney and cardiovascular outcomes with no additional safety concerns. These data support current guideline recommendations to continue SGLT2 inhibitors until dialysis or transplantation.
