Low Doses of Dasiglucagon Consistently Increase Plasma Glucose (PG) Levels in Hypoglycemia and Euglycemia in People with Type 1 Diabetes Mellitus (T1DM)

Abstract

To develop a dual hormone artificial pancreas (DHAP) a liquid stable glucagon component is needed. Currently available glucagon products have limited stability after reconstitution and are therefore not suited for DHAP usage. Dasiglucagon is a novel liquid stable glucagon analog, which does not require mixing prior to use. In this randomized double-blind trial 17 patients with T1DM received four single subcutaneous doses (0.03, 0.08, 0.2 and 0.6 mg) of dasiglucagon (4 mg/ml) under hypoglycemic (plasma glucose (PG) 56-66 mg/dL) or euglycemic (PG 100 mg/dL) conditions. For comparison, identical doses of Lilly GlucagonTM (GLUCA) were investigated at euglycemia. In the euglycemic setting dasiglucagon showed rapid and dose-dependent PG-increases of mean 39, 56, 72 and 80 mg/dL at 30 minutes post-dosing (30, 49 and 71 mg/dl for GLUCA) (Figure). During hypoglycemia, dasiglucagon provided similar PG-increases of 24, 64, 87 and 94 mg/dL 30 minutes post dose and rapidly corrected PG levels to normoglycemia (PG ?70 mg/dL) with a median time of 14, 10, 6 and 6 minutes. In conclusion, low doses of dasiglucagon rapidly and effectively increase PG from euglycemia and hypoglycemia in a titratable manner. Therefore, dasiglucagon should be a good candidate for use in dual-hormone closed-loop AP systems.Figure. Different Doses of Dasiglucagon and GLUCA, PG Levels (Mean ±SEM). Disclosure U. Hovelmann: None. M. Braendholt Olsen: Stock/Shareholder; Self; Novo Nordisk A/S. Employee; Self; Zealand Pharma A/S. U. Mouritzen: Employee; Self; Zealand Pharma A/S. Stock/Shareholder; Self; Novo Nordisk A/S. D. Lamers: None. B. Kronshage: None. T. Heise: Research Support; Self; ADOCIA, Boehringer Ingelheim GmbH, Dance Biopharm, Eli Lilly and Company, Janssen Research & Development, MedImmune, Merck Sharp & Dohme Corp., Mylan, Nordic Bioscience, Novo Nordisk A/S, Poxel SA, Roche Diagnostics Corporation, Saniona, Sanofi, Senseonics, Zealand Pharma A/S. Advisory Panel; Self; Novo Nordisk A/S, Mylan. Speaker's Bureau; Self; Dexcom, Inc., Eli Lilly and Company, Novo Nordisk A/S, Sanofi.