Evidence Grade A — Regulatory approved. 54365 published studies. 584 registered clinical trials.
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Glucagon is a natural hormone produced by the pancreas that raises blood sugar when it drops too low. Pharmaceutical versions are used as emergency rescue treatments for severe hypoglycaemia — dangerously low blood sugar episodes that can cause unconsciousness in people using insulin. Recent innovations including a nasal powder (Baqsimi) and ready-to-use auto-injectors (Gvoke, Zegalogue) have made it much easier to administer in emergencies.
Glucagon is also known by these brand and alternate names:
54,365 published studies: 28383 human, 18217 animal, 4293 in-vitro, 9813 reviews
Glucagon has been available as an emergency injection since the 1960s and remains the standard rescue treatment for severe hypoglycaemia. Recent innovation has focused on making it easier to administer in emergencies. Baqsimi, approved in 2019, was the first needle-free option as a nasal powder. Gvoke, also approved in 2019, eliminated the need to mix and reconstitute the medication before injection — a significant advance since severe hypoglycaemia often impairs the ability to follow complex preparation steps.
Dasiglucagon (Zegalogue), a next-generation stable liquid glucagon approved in 2021, further improved on the convenience of rescue administration. Beyond emergency rescue, glucagon's receptor is now a major research target — dual and triple agonists combining glucagon receptor activity with GLP-1 (such as survodutide and retatrutide) are in advanced clinical trials for obesity and metabolic disease.
When blood sugar drops too low, your pancreas releases glucagon to trigger the liver to release its stored sugar (glycogen) back into the bloodstream. Pharmaceutical glucagon works the same way — it binds to glucagon receptors on liver cells, triggering rapid release of stored sugar. This can raise blood sugar levels within minutes, which is why it is the primary emergency treatment for severe hypoglycaemia. It also relaxes smooth muscle in the digestive tract, which is why it is used as a diagnostic tool during imaging procedures to temporarily slow gut movement.
Emergency glucagon rescue is well-established and life-saving. The major recent advances have focused on making it easier to use under emergency conditions. Traditional glucagon kits required mixing a powder with liquid before injection — a complex process for someone whose family member is unconscious. Baqsimi (nasal powder, 2019) eliminated needles entirely. Gvoke (auto-injector, 2019) eliminated the mixing step. Dasiglucagon/Zegalogue (stable liquid, 2021) demonstrated 99% glucose recovery within 15 minutes. Beyond emergency rescue, the glucagon receptor has become a major target in obesity and metabolic disease research. Dual agonist drugs that combine glucagon receptor activity with GLP-1 activity (such as survodutide) are in late-stage trials for obesity and liver disease, leveraging glucagon's ability to increase energy expenditure alongside GLP-1's appetite-suppressing effects.
PeptideTrace tracks 584 registered clinical trials for Glucagon sourced from ClinicalTrials.gov.
Effect of the Enteric Hormone Glucagon-Like Peptide (GLP-2) on the Intestinal Blood Flow in Patients With Short Bowel Syndrome
Closed-loop Control of Glucose Levels (Artificial Pancreas) for 15 Weeks in Adolescents and Adults With Type 1 Diabetes
Closed-loop Control of Glucose Levels in the Context of Exercise in Adults With Type-1 Diabetes
Glucagon Like Peptides Receptors Expression in the Stomach of Diabetes Type 2
DiaCon Dual-Hormone Closed-Loop Glucose Control
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Health Canada Market Authorisation
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EMA Marketing Authorisation
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Glucagon is a 29-amino-acid endogenous counter-regulatory peptide hormone produced by pancreatic α-cells. Pharmaceutical glucagon is available in multiple formulations: traditional lyophilized powder requiring reconstitution (GlucaGen), a nasal powder (Baqsimi), a ready-to-use liquid-stable injection (Gvoke), and a glucagon analogue (dasiglucagon/Zegalogue).
Glucagon binds the glucagon receptor (GCGR), a class B GPCR on hepatocytes, activating the Gs/adenylyl cyclase/cAMP/PKA cascade. This stimulates hepatic glycogenolysis (breakdown of glycogen to glucose) and gluconeogenesis (synthesis of glucose from non-carbohydrate precursors), rapidly raising blood glucose levels. Efficacy is dependent on adequate hepatic glycogen stores—patients who are fasting, severely malnourished, or have adrenal insufficiency may have attenuated responses. At high doses, glucagon also produces smooth muscle relaxation via cAMP elevation in GI smooth muscle cells.
Glucagon formulations include GlucaGen/Glucagon Emergency Kit (lyophilized, requires reconstitution), Baqsimi (nasal powder 3 mg, approved July 24, 2019—first needle-free rescue glucagon), Gvoke (liquid-stable autoinjector/prefilled syringe, approved September 10, 2019), and Zegalogue/dasiglucagon (glucagon analogue, approved March 22, 2021). All are indicated for the treatment of severe hypoglycemia. Injectable formulations also have a diagnostic indication for inhibition of GI motility during imaging procedures. Baqsimi and Gvoke/Zegalogue represented major advances in usability by eliminating the reconstitution step required with traditional glucagon kits.
Linaclotide is marketed as Linzess (approved August 2012). It is taken as a daily oral capsule on an empty stomach, at least 30 minutes before the first meal. The recommended dose is 290 mcg for IBS-C and 72 or 145 mcg for chronic constipation. In clinical trials, approximately 34% of IBS-C patients met the composite improvement endpoint compared to 17% on placebo. Diarrhoea is the most common side effect (approximately 20%) and the leading reason for discontinuation. Linaclotide has a boxed warning against use in children under 6 years due to deaths in young mice, though no such events have been reported in humans. It competes with plecanatide (which targets the same pathway) and other IBS-C treatments.
Elamipretide (Forzinity) was approved by the FDA for Barth syndrome based on the TAZPOWER trial. The randomised crossover phase (12 patients) did not meet its primary endpoints, but the open-label extension (168 weeks) demonstrated durable improvements in walking distance and muscle strength that formed the basis for approval. Barth syndrome affects approximately 1 in 300,000–400,000 births. A larger Phase III trial in primary mitochondrial myopathy (218 patients, MMPOWER-3) did not meet its primary endpoint, and the drug was not approved for that broader indication. Elamipretide remains approved exclusively for Barth syndrome. See also SS-31 (#158) for the research compound context.
Palopegteriparatide is marketed as Yorvipath (Ascendis Pharma, approved August 2024). It is the first FDA-approved PTH replacement therapy for hypoparathyroidism, a condition that previously had no approved hormone replacement and was managed only with high doses of calcium supplements and active vitamin D — an approach that does not fully normalise calcium metabolism. In the PaTHway trial, 79% of patients achieved independence from calcium and active vitamin D supplements while maintaining normal blood calcium levels, compared to 5% on placebo. This represents a fundamental shift in managing hypoparathyroidism — from supplementation to actual hormone replacement. Patients also showed improvements in kidney function markers and bone metabolism parameters.
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