From the Guidelines
Glucagon is a hormone that raises blood sugar levels by stimulating the breakdown of stored glycogen into glucose and promoting the production of new glucose from non-carbohydrate sources, and its use is indicated for the treatment of hypoglycemia in individuals unable or unwilling to consume carbohydrates by mouth, as stated in the 2024 standards of care in diabetes 1. When blood glucose levels fall, glucagon is released into the bloodstream and travels to the liver, where it triggers the breakdown of stored glycogen into glucose through a process called glycogenolysis. Some key points about glucagon include:
- It stimulates gluconeogenesis, the production of new glucose from amino acids and other non-carbohydrate sources
- It reduces glucose consumption by tissues and promotes the breakdown of fats for energy
- It is part of the body's natural regulatory system to maintain blood glucose within a normal range
- In medical settings, injectable glucagon is used as an emergency treatment for severe hypoglycemia, especially in diabetic patients who are unconscious or unable to consume sugar orally, with newer formulations such as intranasal and ready-to-inject preparations being preferred due to their ease of administration 1. The use of glucagon is essential for individuals treated with insulin or at high risk of hypoglycemia, and clinicians should routinely review their access to glucagon and instruct those in close contact with them on its use, including where the product is kept and when and how to administer it, as emphasized in the 2024 standards of care in diabetes 1.
From the FDA Drug Label
Glucagon increases blood glucose concentration by activating hepatic glucagon receptors, thereby stimulating glycogen breakdown and release of glucose from the liver. Glucagon works by:
- Activating hepatic glucagon receptors
- Stimulating glycogen breakdown
- Releasing glucose from the liver 2
From the Research
How Glucagon Works
- Glucagon is an emergency medication that can quickly raise glucose levels in people who are unconscious or unable to consume glucose due to severe hypoglycemia 3.
- It is used to resolve severe hypoglycemia in unconscious patients with diabetes, requiring third-party assistance 4.
- Glucagon can be administered through different routes, including intramuscular (i.m.), subcutaneous (s.c.), and intravenous (i.v.) injection 5.
- The efficacy of glucagon in increasing blood glucose levels is not different when administered via the i.m. or s.c. route, but it is most efficient when injected i.v. in cases of severe hypoglycemia 5.
Comparison of Glucagon Administration Routes
- Intramuscular glucagon is valuable in the treatment of severe hypoglycemia outside of the hospital, with the advantage of ease of administration and a lower incidence of serious adverse effects 6.
- Intranasal (IN) glucagon has been shown to be equally effective as injected intramuscular/subcutaneous (IM/SC) glucagon in treating hypoglycemia in type 1 diabetes patients 4.
- A comparison of glucagon and glucose in prehospital hypoglycemia found that intravenous glucose is the treatment of choice, but glucagon should also be available for intramuscular use when intravenous access is not possible 7.
Efficacy and Safety of Glucagon
- Glucagon has been underutilized due to the lack of confidence or ability to administer in emergency situations, but new formulations such as nasal powder glucagon and liquid-stable glucagon have become available 3.
- The effectiveness of glucagon in resolving hypoglycemia has been demonstrated in several studies, with no significant difference in efficacy between different administration routes 5, 4.
- The safety of glucagon has also been evaluated, with a low incidence of serious adverse effects reported 6, 7.