Sodium-glucose Cotransporter 2 Inhibition in Patients With Type 2 Diabetes and Chronic Kidney Disease Experiencing a Deterioration in Estimated Glomerular Filtration Rate to <20 mL/min/1.73 m2.

BACKGROUND

Clinical practice guidelines recommend the initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors when the estimated glomerular filtration rate (eGFR) is ≥20 mL/min/1.73 m2. Although continuing SGLT2 inhibitors when the eGFR falls to <20 mL/min/1.73 m2 is recommended, data on the efficacy and safety of SGLT2i in this setting are limited.

METHODS AND

RESULTS

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/1.73 m2, efficacy and safety outcomes, and treatment with canagliflozin. Among 4401 randomized participants, 443 (10.1%) experienced eGFR deterioration to <20 mL/min/1.73 m2 at least once in follow-up. These participants experienced a higher risk of the primary composite outcome (hazard ratio [HR] 10.68, 95% confidence interval [CI] 8.50-13.41, P < .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 the eGFR to <20 mL/min/1.73 m2 (PInteraction = .18). Although the incidence of adverse outcomes was higher among participants whose eGFR fell to <20 mL/min/1.73 m2, event rates remained similar between treatment groups irrespective of an eGFR decline to <20 mL/min/1.73 m2.

CONCLUSIONS

In patients with type 2 diabetes and chronic kidney disease whose eGFR fell to <20 mL/min/1.73 m2, continuation of canagliflozin was associated with a 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.