Glucagon is one of the oldest peptide hormones used in medicine, and it works in the opposite direction from the GLP-1 drugs that dominate today's headlines. Where semaglutide and tirzepatide lower blood sugar, glucagon raises it, and that makes it a critical rescue treatment for severe hypoglycemia.
What It Is
Glucagon is a 29-amino-acid peptide hormone produced by the alpha cells of the pancreas. It is the body's main counter-regulatory hormone to insulin: when blood glucose drops too low, the pancreas releases glucagon, which signals the liver to break down stored glycogen and produce new glucose, raising blood sugar back toward a normal range.
Regulatory Status
Glucagon has been FDA-approved for decades as an emergency treatment for severe hypoglycemia, most often in people with diabetes who take insulin. Older formulations required mixing a powder with a diluent before injection, a process that could be difficult to perform correctly in an emergency. Newer, ready-to-use formulations have since been approved, including Baqsimi, a nasal powder spray, Gvoke, a prefilled auto-injector or syringe, and Zegalogue, a prefilled pen containing dasiglucagon, a stabilized glucagon analog. All of these are FDA-approved prescription products.
What the Research Shows
Glucagon's glucose-raising mechanism is well established through decades of human research and clinical use, unlike many research-chemical peptides discussed elsewhere on this site. Clinical trials supporting the newer ready-to-use formulations focused on demonstrating that a bystander, such as a family member or coworker without medical training, could administer the correct dose quickly and effectively compared with older reconstitution kits, and that the resulting rise in blood glucose was comparable.
Safety Considerations
Nausea and vomiting are common after glucagon administration, since the hormone also affects gastrointestinal motility. Glucagon depends on the liver having glycogen stores to break down, so it is less effective in situations where those stores are depleted, including prolonged fasting, adrenal insufficiency, chronic alcohol use, or repeated recent hypoglycemic episodes. It also requires caution in people with insulinoma or pheochromocytoma, where it can trigger problematic hormone surges. Glucagon is a rescue treatment for an emergency, not a chronic therapy, and anyone who experiences severe hypoglycemia should follow up with a doctor about their overall treatment plan.
An Unexpected Second Act
Glucagon's role in medicine has recently expanded in a counterintuitive direction. Several next-generation obesity and diabetes drugs now in development, including survodutide, mazdutide, cotadutide, and retatrutide, are deliberately engineered to activate the glucagon receptor alongside the GLP-1 receptor, rather than avoiding it. In that combination, glucagon receptor activity appears to increase energy expenditure and fat oxidation, contributing to weight loss, while the accompanying GLP-1 or GIP agonism helps offset glucagon's blood-sugar-raising tendency. The comparison article on this site covering glucagon versus GLP-1 goes into more detail on how that balance is thought to work.
The Bottom Line
Glucagon is a well-understood, FDA-approved peptide hormone with a clear, narrow emergency role: reversing severe hypoglycemia quickly. Its reappearance as a deliberate ingredient in dual- and triple-agonist obesity drugs is one of the more interesting developments in peptide pharmacology, turning a decades-old rescue hormone into a building block for an entirely different therapeutic goal.