Glucagon: Uses, Mechanism, and Reported Side Effects

Key takeaways

• Glucagon is FDA-approved to treat severe hypoglycemia in people with diabetes and as a diagnostic aid during GI imaging.
• It works by activating hepatic glucagon receptors, prompting the liver to break down glycogen and release glucose.
• More than 3,300 registered trials have studied glucagon or related agents across diabetes and endocrine research.
• Reported adverse events span drug ineffectiveness, breathing difficulty, kidney injury, low blood pressure, and low blood sugar.
• It carries no boxed warning on its current label.

What Glucagon Is

Glucagon is a peptide hormone marketed under the brand name Glucagon. It is classified as an antihypoglycemic agent and a gastrointestinal motility inhibitor.

According to its label, glucagon raises blood glucose by activating glucagon receptors in the liver. This stimulates the breakdown of stored glycogen and the release of glucose into the bloodstream. The label notes that adequate liver glycogen stores are necessary for this antihypoglycemic effect to occur. Separately, glucagon relaxes smooth muscle in the stomach, duodenum, small bowel, and colon, which underlies its use in GI imaging.

What Glucagon Is Approved For

Glucagon for Injection has two approved uses. The first is treatment of severe hypoglycemia in pediatric and adult patients with diabetes mellitus. The second is as a diagnostic aid during radiologic examinations, where it temporarily inhibits movement of the gastrointestinal tract in adult patients. No boxed warning is present on the current label.

What the Evidence Shows

More than 3,300 trials have been registered involving glucagon and related compounds. A completed trial examined closed-loop glucagon administration for treating hypoglycemia. Another completed phase 2/3 trial evaluated dasiglucagon, a glucagon analog, in children with congenital hyperinsulinism. Additional research has studied related glycemic control agents, such as a completed phase 3 trial of the GLP-1 agonist lixisenatide in type 2 diabetes.

Reported Side Effects

FAERS data reflect adverse event reports, not confirmed incidence or causation. The most frequently reported issue is drug ineffectiveness (381 reports), followed by dyspnoea, or difficulty breathing (367). Kidney-related and cardiovascular reports are also common, including acute kidney injury (320) and hypotension (293). Metabolic and general reports include hypoglycaemia (271), condition aggravated (253), toxicity to various agents (238), and nausea (232).