Introduction and Objective: Many people living with T1D do not achieve glycemic targets, and the risk of severe hypoglycemia persists. HDV-L restores postprandial hepatic glycogen storage by presenting insulin to hepatocyte receptors as a dense molecular aggregate, improving receptor signaling. The OPTI-2 study evaluated the impact of HDV-L on A1C and hypoglycemia risk.Methods: In a 25-week double-blind Phase 2b trial, 226 adults with T1D treated with MDI were randomized 1:1 to bolus insulin with insulin lispro (L) or HDV-L with CGM for 12 weeks of optimization followed by13 weeks of maintenance therapy.Results: Baseline characteristics were comparable (age 19-76 years and A1C 5.7-9.5%. HDV-L was non-inferior to L in reducing A1C (Table). A trend in hypoglycemia reduction was observed with HDV-L compared to L during the dose optimization period, and significant hypoglycemia reductions were observed during the maintenance period (Figure). Five L-treated subjects had severe hypoglycemic events compared to 0 with HDV-L (p = 0.0598). Treatment emergent adverse events (TEAE) were similar between groups, but fewer people randomized to HDV-L had serious TEAEs (8 L vs 1 HDL-L. There were no deaths or DKA.Conclusion: HDV-L associated with reductions in clinically meaningful hypoglycemia, including severe hypoglycemia, while preserving glycemic control in people with T1D using MDI. These data support advancement into Phase 3 studies.
K.R. Klein: Consultant; Current; Roche Pharmaceuticals, Novo Nordisk A/S. Advisory Panel; Current; vTv Therapeutics. Consultant; Current; Antag Therapeutics, Metsera. L.K. Billings: Advisory Panel; Current; Novo Nordisk, Lilly, Sanofi, Amgen Inc., Bayer AG. J.B. Buse: Consultant; Current; Aardvark Therapeutics, Altimmune, Alveus Therapeutics, Amgen Inc., Antag Therapeutics, Aqua Medical, AstraZeneca, Boehringer Ingelheim International GmbH. Other – Consultant and clinical trial support; Current; Corcept Therapeutics. Consultant; Ended; Dexcom, Inc. Consultant; Current; Eli Lilly and Company. Consultant; Ended; embecta. Consultant; Current; General Medicines Inc. Other – Consultant and clinical trial support; Current; GentiBio. Consultant; Ended; Insulet Corporation. Consultant; Current; Kayothera. Other – Consultant and stock options; Current; Metsera. Other – Expert witness; Ended; Medtronic. Other – Consultant and investigator; Current; Novo Nordisk. Consultant; Current; Recordati S.p.A, Sparrow Pharmaceuticals. Consultant; Ended; Tandem Diabetes Care, Inc. Consultant; Current; Vertex Pharmaceuticals Incorporated, vTv Therapeutics, Zealand Pharma A/S. S. Garg: Advisory Panel; Current; Abbott Diabetes. Research Support; Current; Eli Lilly and Company. Advisory Panel; Current; Medtronic. Research Support; Current; Dexcom, Inc. Advisory Panel; Current; Roche Diagnostics, Vertex Pharmaceuticals Incorporated, ConvaTec Inc. Research Support; Current; Diasome. R. Weinstock: Research Support; Current; Amgen Inc., Eli Lilly and Company, JDRF, Diasome, DEKA Research and Development, Tandem Diabetes Care, Inc. Research Support; Ended; Kowa Research Institute, Inc. Research Support; Current; National Institutes of Health. Research Support; Ended; Insulet Corporation. Research Support; Current; T1D Exchange. W.B. Geho: Other – Board Member, Chief Scientific Officer; Current; Diasome. Employee; Current; SDG, Inc. H. Plotkin: Employee; Current; Diasome, SDG, Inc. Employee; Ended; Novo Nordisk. D. Muchmore: Stock/Shareholder; Current; Eli Lilly and Company. Advisory Panel; Current; Zucara Therapeutics. Consultant; Current; Diasome. C.E. El Sanadi: None. J. Chapin: Employee; Current; Diasome. Employee; Ended; IQVIA Inc., SDG Inc. J. Ilgenfritz: Consultant; Current; Diasome. R. Geho: Other – Board member, CEO; Current; Diasome. Employee; Current; SDG, Inc. P.S. Strumph: Consultant; Current; Diasome. Other – shareholder; Current; Diasome.
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