Efficacy and safety of sotagliflozin in patients with type 2 diabetes and severe renal impairment

Aims To assess the efficacy and safety of sotagliflozin, a dual inhibitor of sodium‐glucose cotransporter‐1 and ‐2, in adults with type 2 diabetes (T2D) and stage 4 chronic kidney disease (CKD4). Materials and Methods This 52‐week, phase 3, randomized (1:1:1), placebo‐controlled trial evaluated sotagliflozin 200 mg and sotagliflozin 400 mg once daily in 277 patients with T2D and estimated glomerular filtration rate (eGFR) 15 to 30 mL/min/1.73 m2. The primary endpoint was glycated haemoglobin (HbA1c) reduction with sotagliflozin 400 mg versus placebo at 26 weeks. A hierarchical statistical testing approach was used. Results The baseline mean HbA1c was 65 ± 12 mmol/mol (8.1% ± 1.1%), systolic blood pressure (SBP) was 144 ± 15 mmHg, and eGFR was 24 ± 4 mL/min/1.73m2. Placebo‐adjusted changes with sotagliflozin 400 mg were –3 mmol/mol (−0.3%; 95% confidence interval –7 to 0.6 [−0.6 to 0.05]; P = 0.096) and –8 mmol/mol (−0.7%; –13 to –3 [−1.2 to −0.2]; P = 0.003) in HbA1c at Weeks 26 and 52, respectively, −1.5 kg (−3.0 to −0.1) in body weight at Week 26, −5.4 mmHg (−9.4 to −1.3) in SBP at Week 12, and −0.3 mL/min/1.73 m2 (−2.1 to 1.6; P = 0.776) in eGFR at Week 52. Over 52 weeks, 11.8%, 5.4% and 3.3% of patients receiving placebo and sotagliflozin 200 and 400 mg, respectively, required rescue therapy for hyperglycaemia. Adverse events (AEs) occurred in 82.8%, 86.2% and 81.1% of patients and serious cardiovascular AEs occurred in 12.9%, 3.2% and 4.4% of patients in the placebo and sotagliflozin 200 and 400 mg groups, respectively. Conclusions After 26 weeks, HbA1c reductions with sotagliflozin were not statistically significant versus placebo in adults with T2D and CKD4. The 52‐week safety profile was consistent with results of the SCORED outcomes trial (NCT03242018).