Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD
Vikas S. Sridhar, Ayodele Odutayo, Subhash Vishal Garg, Thomas Danne, Alessandro Doria, Michael Mauer, Michael J. Davies, Phillip Banks, Manon Girard, David Z.I. Cherney
Abstract
Key Points Poor glycemic control in type 1 diabetes and CKD is associated with a higher risk of CKD progression. In a subgroup of inTandem participants with type 1 diabetes and CKD, adding sotagliflozin to insulin reduced HbA1c, body weight, and systolic BP without increasing severe hypoglycemia, compared with adding placebo. In participants with type 1 diabetes and CKD, sotagliflozin did not significantly increase the risk of DKA, however, there were a small number of diabetic ketoacidosis events. Background This analysis evaluated the efficacy and safety of sotagliflozin, a dual sodium-glucose cotransporter 1 and 2 inhibitor, added to insulin in patients with type 1 diabetes and CKD. Methods We used data from the 52-week pooled inTandem 1 and 2 trials and the 24-week inTandem 3 trial to assess the effects of sotagliflozin (200 mg [inTandem 1 and 2 only] or 400 mg daily) versus placebo on glycated hemoglobin (HbA1c; primary end point), body weight, systolic BP, insulin dose, and safety end points including adjudicated severe hypoglycemia and diabetic ketoacidosis (DKA), stratified by CKD. Results CKD was identified in 237/1575 inTandem 1 and 2 participants and 228/1402 inTandem 3 participants. At week 24, significant, placebo-adjusted reductions in HbA1c were observed—inTandem 1 and 2: non-CKD subgroup (sotagliflozin 200 mg: −0.4%, 95% confidence interval [CI], −0.4 to −0.3; 400 mg: −0.4%, 95% CI, −0.5 to −0.3) and CKD subgroup (sotagliflozin 200 mg: −0.4%, 95% CI, −0.6 to −0.1; 400 mg: −0.3%, 95% CI, −0.5 to −0.1). For systolic BP, there was a significant reduction at week 24 with sotagliflozin in the non-CKD subgroup, but no effect in the CKD subgroup in inTandem 1 and 2. At week 52, the incidence of severe hypoglycemia was lower with sotagliflozin (7% on 200 mg and 4% on 400 mg) compared with placebo (17%) in the CKD subgroup of inTandem 1 and 2, whereas the incidence of severe hypoglycemia was 5%–6% across non-CKD subgroups. The incidence of adjudicated DKA at week 52 was 1%, 5%, and 3% for placebo, 200, and 400 mg in the CKD subgroup compared with 0%, 3%, and 4% in the non-CKD subgroup, respectively. The results were generally similar in inTandem 3, except systolic BP was significantly reduced with sotagliflozin versus placebo in CKD and non-CKD subgroups. Conclusions In participants with type 1 diabetes and CKD, sotagliflozin treatment had similar HbA1c, body weight, and systolic BP lowering effects as in participants with type 1 diabetes without CKD. In addition, sotagliflozin was associated with a lower to neutral risk of severe hypoglycemia and did not significantly increase the risk of DKA among a small number of DKA events. Clinical Trial registration numbers: NCT02384941, NCT02421510, NCT02531035.