Pharmacokinetic and Pharmacodynamic Characteristics of Dasiglucagon, a Novel Soluble and Stable Glucagon Analog
| Autor: | Ulrike Hövelmann, Daniela Lamers, Britta Væver Bysted, Tim Heise, Francesca Macchi, Birgit Kronshage, Daniél Vega Møller, Ulrik Mouritzen |
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| Rok vydání: | 2017 |
| Předmět: |
Adult
Blood Glucose Male Adolescent Injections Subcutaneous Endocrinology Diabetes and Metabolism 030209 endocrinology & metabolism Pharmacology Hypoglycemia Glucagon Young Adult 03 medical and health sciences 0302 clinical medicine Double-Blind Method Pharmacokinetics Diabetes mellitus Internal Medicine medicine Humans Hypoglycemic Agents Insulin 030212 general & internal medicine Adverse effect Advanced and Specialized Nursing Type 1 diabetes Dose-Response Relationship Drug business.industry medicine.disease Diabetes Mellitus Type 1 Tolerability Pharmacodynamics Female business Half-Life |
| Zdroj: | Diabetes Care. 41:531-537 |
| ISSN: | 1935-5548 0149-5992 |
| DOI: | 10.2337/dc17-1402 |
| Popis: | OBJECTIVE Treatment of severe hypoglycemia outside of the hospital setting is limited to glucagon formulations requiring reconstitution before use, which may lead to erroneous or delayed glucagon administration. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and safety and tolerability of different doses of dasiglucagon, a novel soluble glucagon analog, with approved pediatric and full doses of GlucaGen in insulin-induced hypoglycemia in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS In this single-center, randomized, double-blind trial, 58 patients with type 1 diabetes received single subcutaneous injections of 0.1, 0.3, 0.6, or 1.0 mg dasiglucagon or 0.5 or 1.0 mg GlucaGen in a state of hypoglycemia (blood glucose target 55 mg/dL) induced by an intravenous insulin infusion. RESULTS Dasiglucagon demonstrated a dose-dependent and rapid increase in plasma concentrations, reaching a maximum at ∼35 min with a half-life of ∼0.5 h. Dasiglucagon rapidly increased plasma glucose (PG) by ≥20 mg/dL (9–14 min) to PG ≥70 mg/dL (within 6–10 min), similar to GlucaGen, but with a longer-lasting and greater effect on PG. All patients on both treatments reached these end points within 30 min (predefined success criteria). Both treatments were well tolerated. Nausea was the most frequent adverse event, occurring at a similar rate (44–56%). CONCLUSIONS Dasiglucagon was well tolerated and showed an early PD response similar to that of GlucaGen at corresponding doses, suggesting comparable clinical effects of the two glucagon formulations. Dasiglucagon has the potential to become an effective and reliable rescue treatment for severe hypoglycemia in a ready-to-use pen. |
| Databáze: | OpenAIRE |
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