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Feb 18, 2019

12th International Conference on Advanced Technologies & Treatments for Diabetes

01 - SMALL DOSES OF DASIGLUCAGON CONSISTENTLY INCREASE PLASMA GLUCOSE (PG) LEVELS FROM HYPOGLYCEMIA AND EUGLYCEMIA IN PEOPLE WITH TYPE 1 DIABETES MELLITUS (T1DM)

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hypoglycemia

glucagon

diabetes mellitus

dual-hormone artificial pancreas system

euglycemia

Abstract

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Abstract

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Keywords

hypoglycemia

glucagon

diabetes mellitus

dual-hormone artificial pancreas system

euglycemia

Abstract

SMALL DOSES OF DASIGLUCAGON CONSISTENTLY INCREASE PLASMA GLUCOSE (PG) LEVELS FROM HYPOGLYCEMIA AND EUGLYCEMIA IN PEOPLE WITH TYPE 1 DIABETES MELLITUS (T1DM) Ulrike Hövelmann1, Minna Braendholt Olsen2, Ulrik Mouritzen2, Daniela Lamers1, Birgit Kronshage1, Tim Heise1 1Profil, Neuss, Germany 2Zealand Pharma A/S, Glostrup, Denmark Background and Aims: Currently available glucagon formulations are of limited stability, which hinders their use in dual-hormone artificial pancreas (DHAP) systems to prevent hypoglycemia. We characterized the pharmacokinetic and pharmacodynamic properties of dasiglucagon, a novel, stable and liquid formulated glucagon analog and promising candidate for use in DHAP systems. Method: 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 formulation) under hypoglycemic (PG 56-66 mg/dL) or euglycemic (PG 100 mg/dL) conditions. For comparison, three doses (0.03, 0.08 and 0.2 mg) of a commercial glucagon (Glucagon, Eli Lilly) were investigated at euglycemia. Result: Dasiglucagon showed dose-dependent and rapid PG-increases across all doses (mean increase 30 min post-dosing 24-94 mg/dl from hypoglycemia and 39-80 mg/dL from euglycemia, compared to 30-71 mg/dl with Glucagon) (figure). Median time to increase in PG by >20 mg/dL was less than 20 min (18-19.5 min) with 0.03 mg dasiglucagon and 9-15 min with higher doses (Glucagon 13-14 min). In hypoglycemia, 0.03 and 0.08 mg dasiglucagon re-established normoglycemia (PG ≥70 mg/dL) within median times of 14 and 10 min, respectively. All patients achieved a PG ≥70 mg/dL within 30 minutes post-dose at dose levels of 0.08 mg and above. Conclusion: Dasiglucagon rapidly and effectively increases PG even in low doses and in a titratable and dose-dependent fashion from both hypoglycemia and euglycemia. The PD profile described supports dasiglucagon as a promising candidate for use in dual-hormonal closed-loop AP systems.

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© Copyright 2019 Morressier GmbH.
All rights reserved.