Disease Background

Hypoglycemia is defined by: one, the development of neurogenic (autonomic) or neuroglycopenic symptoms; two, a low plasma glucose level (< 4.0 mmol/L for people with diabetes treated with insulin or an insulin secretagogue); and three, symptoms responding to the administration of carbohydrate.¹ Neurogenic (autonomic) symptoms include trembling, palpitations, sweating, anxiety, hunger, nausea, and tingling. Neuroglycopenic symptoms include difficulty concentrating, confusion, weakness, drowsiness, vision changes, difficulty speaking, headache, and dizziness.¹

The severity of hypoglycemia is defined by clinical manifestations. Severe hypoglycemia is defined in recent Diabetes Canada Guidelines as hypoglycemia requiring the assistance of another person.¹ Unconsciousness may occur in severe hypoglycemia and plasma glucose is typically less than 2.8 mmol/L. Hypoglycemia is more frequent in people with T1D compared to people with T2D managed by insulin.^1,2

Dangerous situations may arise when a person is experiencing hypoglycemia (e.g., while driving or operating machinery). Prolonged coma is sometimes associated with transient neurological symptoms, such as paresis, convulsions, and encephalopathy. Long-term complications of severe hypoglycemia include mild intellectual impairment and hemiparesis. There are some data suggesting that there is an association between severe hypoglycemia and cognitive disorders, though causality remains uncertain.^1–3

Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Baqsimi (glucagon intranasal powder) is indicated for the treatment of severe hypoglycemic reactions which may occur in the management of insulin-treated patients with diabetes mellitus, when impaired consciousness precludes oral carbohydrates. It is supplied as a powder in a single use nasal delivery device. Inhalation is not required by the patient. It is administered as a single 3 mg dose in both adults and children.⁴

Standards of Therapy

Treating severe hypoglycemia requires the assistance of another person to administer carbohydrate, glucagon, or other resuscitative actions. Patients with IV access can be given 25 g of 50% glucose (dextrose) intravenously.² Alternatively, glucagon can be administered intramuscularly, subcutaneously, or intranasally. The clinical expert consulted by CADTH for this review indicated that one dose is usually adequate for patient recovery from severe hypoglycemia. Administration of glucagon usually leads to recovery of consciousness within approximately 15 minutes, and it may be followed by nausea or vomiting.^1,2 Glucagon administration is often followed by glucose administration either by infusion, or orally if level of consciousness permits.^1,2 Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and the release of glucose from the liver. Hepatic stores of glycogen are necessary for glucagon to produce an antihypoglycemic effect.⁴

Drug

Glucagon powder for intranasal administration (Baqsimi) is approved for the treatment of severe hypoglycemic reactions which may occur in the management of insulin-treated patients with diabetes mellitus, when impaired consciousness precludes oral carbohydrates.⁴ It received a Notice of Compliance from Health Canada on September 25, 2019. Intranasal glucagon (Baqsimi) received a Health Canada drug schedule of “ethical” (non-prescription status), which is the same category as many insulin products and epinephrine autoinjectors.¹²

No glucagon product has previously been reviewed through the CADTH Common Drug Review process. The sponsor requested that intranasal glucagon be reimbursed for the same population as stated in the Health Canada indication.

Table 3 summarizes the characteristics of intranasal glucagon and its relevant comparator, glucagon for parenteral administration.

Table 3

Key Characteristics of Glucagon Products.