Indications
Dasiglucagon is an antihypoglycemic agent approved for the management of severe hypoglycemia in both pediatric and adult patients with diabetes, specifically those aged six years and older.
Pharmacodynamics
Dasiglucagon functions by elevating blood glucose levels significantly in both normal and hypoglycemic states. In clinical studies involving adult patients with type 1 diabetes, the mean increase in blood glucose from baseline at 90 minutes post-administration was 168 mg/dL. For pediatric patients, aged seven to seventeen years, the administration of dasiglucagon led to a mean increase in blood glucose of 162 mg/dL within 60 minutes.
Absorption
Following a subcutaneous injection of 0.6 mg dasiglucagon, the average peak plasma concentration recorded was 5110 pg/mL (1510 pmol/L), with a median time to reach this concentration (Tmax) of 35 minutes. In pediatric patients with type 1 diabetes, the mean peak plasma concentration was slightly lower, at 3920 pg/mL, occurring approximately 21 minutes post-administration. Notably, dasiglucagon's absorption rate surpasses that of conventional reconstituted glucagon formulations.
Metabolism
The metabolism of dasiglucagon mirrors that of endogenous glucagon, involving proteolytic degradation pathways within the blood, liver, and kidneys. This pathway ensures efficient processing of dasiglucagon in the body.
Mechanism of Action
Dasiglucagon is a glucagon analog that functions by increasing blood glucose levels, akin to the body's natural glucagon. It operates through the same mechanism as endogenous glucagon by binding to glucagon receptors, which are G-protein-coupled receptors found throughout the body. Upon binding to these receptors in the liver, dasiglucagon activates Gsα and Gq proteins, which in turn stimulate adenylate cyclase. This activation elevates intracellular levels of cyclic AMP, prompting glycogenolysis and gluconeogenesis in the liver. The glucose released from hepatic glycogen stores is essential for dasiglucagon's ability to counteract hypoglycemia, highlighting the importance of these stores for its clinical efficacy.
