1220-P: Sotagliflozin Leads to Lower Rates of Clinically Relevant Hypoglycemic Events at Any HbA1c Level at 52 Weeks in Adults with T1D

Abstract

Hypoglycemia (HYPO) is a major barrier in achieving optimal glycemic control in T1D. Intensifying insulin therapy to lower HbA1c is frequently accompanied by an increased risk of HYPO. In two 52-week phase 3 studies (inTandem1 and 2), sotagliflozin (SOTA), a dual SGLT1 and 2 inhibitor as adjunct to optimized insulin therapy, demonstrated significant reduction in HbA1c and body weight without increasing the risk of severe hypoglycemia compared with placebo (PBO) in adults with T1D. To further evaluate the HYPO profile of SOTA added to insulin, we analyzed rates of confirmed HYPO (level 1, glucose ≤70 mg/dL in the study) and clinically important HYPO (level 2, glucose ≤55 mg/dL in the study) in a patient-level pooled analysis (n=1,368) using a negative binomial model adjusted for HbA1c at week 52. Rates of level 1 HYPO events per patient year were 99.48, 77.14, and 77.14 for PBO, SOTA 200mg, and 400mg, respectively (P<0.0001 vs. PBO for both doses). Significantly lower rates (P<0.0001 vs. PBO for both doses) of level 2 HYPO were also observed (19.69, 14.22, and 13.86 for PBO, SOTA 200mg, and 400mg, respectively). HYPO rate reduction was more pronounced at lower HbA1c with SOTA vs. PBO (Figure). In conclusion, at week 52 overall level 1 and 2 HYPO event rates were 22.5-30% lower with SOTA when used as adjunct to optimized insulin therapy vs. PBO and were reduced at any HbA1c level especially at lower HbA1c values. Disclosure T. Danne: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis. Speaker's Bureau; Self; Dexcom, Inc. J. Pettus: Advisory Panel; Self; Diasome Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; MannKind Corporation. A. Giaccari: Advisory Panel; Self; Sanofi. Board Member; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp., Sanofi. B. Cariou: Board Member; Self; Novo Nordisk A/S, Regeneron Pharmaceuticals. Consultant; Self; GENFIT, Sanofi-Aventis. Research Support; Self; Amgen Inc., Pfizer Inc. Speaker's Bureau; Self; Abbott, Akcea Therapeutics, Merck Sharp & Dohme Corp. H.W. Rodbard: Advisory Panel; Self; Bayer US, Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk Inc., Sanofi. Consultant; Spouse/Partner; Eli Lilly and Company. Consultant; Self; Gan & Lee Pharmaceuticals. Research Support; Self; Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. Speaker's Bureau; Self; Merck & Co., Inc., Novo Nordisk Inc. S.A. Weinzimer: Consultant; Self; Eli Lilly and Company, Sanofi. Consultant; Spouse/Partner; Tandem Diabetes Care. Consultant; Self; Zealand Pharma A/S. Speaker's Bureau; Self; Insulet Corporation, Medtronic MiniMed, Inc., Tandem Diabetes Care. Stock/Shareholder; Self; InsuLine Medical Ltd. M. Bonnemaire: Employee; Self; Sanofi. S. Sawhney: Stock/Shareholder; Spouse/Partner; AstraZeneca, Gilead Sciences, Inc., GlaxoSmithKline plc., Merck & Co., Inc., Pfizer Inc. S. Wang: Employee; Self; Sanofi US. R. Castro: Employee; Self; Sanofi US. S.K. Garg: Advisory Panel; Self; Eli Lilly and Company, Roche Pharma, Sanofi-Aventis, Zealand Pharma A/S. Research Support; Self; Eli Lilly and Company, WebMD. Funding Lexicon Pharmaceuticals Inc.; Sanofi