Safety and Tolerability of Sotagliflozin Among Kidney Transplant Recipients.

Background: Sodium-glucose cotransporter inhibitors (SGLTi) slow chronic kidney disease progression and reduce kidney failure events. Kidney transplant recipients (KTRs) remain at high risk for these outcomes. SGLTi cause an initial and sustained decline in estimated glomerular filtration rate (eGFR) and have a higher risk of urogenital infection, both of which are major concerns for KTRs. We sought to (1) assess the reversibility of eGFR changes and (2) explore safety and tolerability using sotagliflozin, a dual SGLT1/2 inhibitor.

Methods: We enrolled stable KTRs in a 16-wk open-label trial of sotagliflozin (12 wk on-drug and 4 wk off-drug) to assess the reversibility of eGFR changes. We assessed whether patient awareness of eGFR changes altered rates of withdrawal by randomizing participants to either (1) unlimited access to all study-related eGFR measurements or (2) limited access, that is, only when eGFR declined to >25% from baseline.

Results: Forty patients were randomized. The mean age was 56 ± 15 y; the mean baseline eGFR was 64 ± 21 mL/min/1.73 m2. After 1 wk, change in eGFR from baseline was -4.6 ± 6.5 mL/min/1.73 m2 (-6.9 ± 9.5%). After washout, eGFR improved to -2.0 ± 6.3 mL/min/1.73 m2 (-2.4 ± 11%), with 73% of patients within 10% of baseline eGFR or higher. Limited versus unlimited access to eGFR measurements did not affect protocol completion (P = 0.34). Sotagliflozin was generally well tolerated, but 4 patients were withdrawn due to adverse events, with none due to decline in eGFR.

Conclusions: Among stable KTRs, sotagliflozin caused an initial decline in eGFR of similar magnitude to patients with chronic kidney disease, with reversibility upon withdrawal. Access to follow-up eGFR measurements did not affect study adherence.