Balancing the Risk of DKA and Severe Hypoglycemia with Sotagliflozin in Adults with Type 1 Diabetes

Background: DKA and severe hypoglycemia (SH) are the 2 most important acute complications of type 1 diabetes (T1D). SGLT inhibitors are associated with an increased risk of ketosis and DKA. Sotagliflozin (SOTA), a dual SGLT 1 and 2 inhibitor, has been shown to reduce the incidence of documented hypoglycemia and SH as adjunct to insulin therapy in T1D. The objective was to determine if the increased risk of DKA with SOTA was offset by the reduction of SH. Methods: Data were pooled from the inTandem 1 and 2, 52-week, placebo (PBO)-controlled studies in adults with T1D (N=1575). Events of DKA and SH were adjudicated by an IRC. Incidence and exposure-adjusted incidence rates (EAIR) were calculated along with numbers needed to treat or harm (NNT/NNH). Results: A higher incidence of adjudicated DKA was seen with SOTA 200 and 400 mg (2.9 and 3.8%) compared to PBO (0.2%). However, SOTA was associated with a lower rate of hypoglycemia events with blood glucose levels ≤55 mg/dL and a lower incidence of adjudicated SH with SOTA 200 and 400 mg (5.7 and 4.4%) compared with PBO (7.4%). The absolute risk difference in EAIR between SOTA and PBO was 2.9 to 4.0 events per 100 patient-yr for DKA and -1.9 to -3.4 events per 100 patient-yr for SH (Figure). NNH for DKA (28) was similar to the NNT for SH (33) with SOTA 400 mg. Conclusions: With SOTA added to insulin, the increase in DKA was similar in magnitude to the decrease in SH in adults with T1D. Disclosure J. Pettus: Consultant; Self; Diasome Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., MannKind Corporation, Novo Nordisk Inc., Sanofi. B. Cariou: Advisory Panel; Self; Bristol-Myers Squibb, Gilead Sciences, Inc., Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis. Board Member; Self; GENFIT. Research Support; Self; Amgen, Regeneron Pharmaceuticals. Speaker’s Bureau; Self; Abbott, AstraZeneca. S. Sawhney: None. P.L. Banks: Employee; Self; Lexicon Pharmaceuticals, Inc. M.J. Davies: Employee; Self; Lexicon Pharmaceuticals, Inc. P. Lapuerta: Employee; Self; Lexicon Pharmaceuticals, Inc. Stock/Shareholder; Self; Lexicon Pharmaceuticals, Inc.