Efficacy and Safety of Sotagliflozin in Patients with Type 1 Diabetes and CKD.

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.