1084-P: Divergent Hypoglycemic Effects of Hepatic Directed Prandial Insulin: A 6-Month Study in Type 1 Diabetes Mellitus (T1DM)

Hepatic-directed insulin utilizes a hepatocyte-targeting moiety passively attaching free insulin, improving subcutaneous insulin’s hepatic biodistribution. We assessed injections of HDV-insulin lispro (HDV-L) vs. insulin lispro (LIS) in T1DM in a 26-week, multicenter, randomized, double-blind trial of 176 subjects (randomized 2:1 HDV-L:LIS) with A1C 7.0-10.5% treated with basal insulin glargine or degludec. Primary objective was HDV-L A1C non-inferiority (prespecified margin 0.4%). Mean A1C change to week 26 was -0.09% (HDV-L) and -0.16% (LIS), (estimated treatment difference, HDV-L - LIS: +0.09% [95% CI -0.18 to 0.35]), confirming HDV-L non-inferiority. A1C status modified treatment group effect on “severe” hypoglycemia (subjectively categorized by investigators as “mild,” “moderate,” “severe,” or “life threatening”) incidence (interaction p-value Disclosure D.C. Klonoff: Consultant; Self; EOFlow, Lifecare, Inc., Merck & Co., Inc., Novo Nordisk A/S, Roche Diagnostic USA, Voluntis USA. B.W. Bode: Consultant; Self; ADOCIA, Lexicon Pharmaceuticals, Inc., Novo Nordisk Inc. Research Support; Self; Becton, Dickinson and Company, Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Eyenuk Inc., Insulet Corporation, National Institutes of Health, Novo Nordisk Inc., Sanofi Research & Development, Senseonics, Xeris Pharmaceuticals, Inc. Speaker9s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US, Senseonics. Stock/Shareholder; Self; AgaMatrix, Glytec, LLC. N.J. Cohen: None. W. Geho: Board Member; Self; Diasome Pharmaceuticals, Inc. D.B. Muchmore: Consultant; Self; ADOCIA, Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc., Zucara Therapeutics Inc. Stock/Shareholder; Self; Capillary Biomedical, Inc., Diasome Pharmaceuticals, Inc. Funding JDRF