Peptide Schedule
Glucagon (GlucaGen)29 residuesHSQGTFTSDYSKYLDSRRAQDFVQWLMNTEach bubble = one amino acid. Size = residue mass. Color = chemical class.Glucagon (GlucaGen)
Benefits
About Glucagon (GlucaGen)
Glucagon is a naturally occurring 29-amino-acid peptide hormone secreted by the alpha cells of the pancreatic islets of Langerhans. It serves as the primary counter-regulatory hormone to insulin, playing a critical role in glucose homeostasis by raising blood glucose levels when they fall dangerously low. Glucagon was first crystallized by Staub in 1955 and has been used clinically for decades as the standard emergency treatment for severe hypoglycemia. The recombinant DNA-derived form, marketed as GlucaGen by Novo Nordisk and as the Glucagon Emergency Kit by Eli Lilly, received FDA approval for the treatment of severe hypoglycemia. More recently, Eli Lilly introduced Baqsimi, the first nasally administered glucagon approved by the FDA in 2019, providing a needle-free alternative for emergency hypoglycemia rescue. Xeris Pharmaceuticals also launched Gvoke, a room-temperature-stable, ready-to-use liquid glucagon in prefilled syringe and autoinjector formats. Glucagon acts primarily on the liver, where it binds to the glucagon receptor (GCGR), a G protein-coupled receptor, triggering a cascade that activates adenylyl cyclase, increases intracellular cyclic AMP (cAMP), and activates protein kinase A (PKA). This stimulates glycogenolysis — the breakdown of glycogen into glucose — and enhances gluconeogenesis, the de novo synthesis of glucose from non-carbohydrate precursors. The net result is a rapid and significant increase in blood glucose concentration, typically restoring consciousness within 10 to 15 minutes of administration. Beyond hypoglycemia rescue, glucagon is also FDA-approved as a diagnostic aid during radiologic examination of the gastrointestinal tract, where it is used to temporarily inhibit GI motility. Its safety profile is well-established, with nausea and vomiting being the most common adverse effects. Glucagon remains an essential component of diabetes emergency preparedness, and newer formulations have significantly improved usability for caregivers and first responders.
Who Should Consider Glucagon (GlucaGen)
- Type 1 diabetes patients at risk of severe hypoglycemia
- Type 2 diabetes patients on insulin or sulfonylureas
- Pediatric diabetes patients
- Caregivers and family members of insulin-dependent diabetics
- Emergency medical services and first responders
How Glucagon (GlucaGen) Works
Glucagon exerts its effects by binding to the glucagon receptor (GCGR), a class B G protein-coupled receptor predominantly expressed on hepatocytes. Upon ligand binding, the receptor activates the stimulatory G-alpha subunit (Gs), which in turn stimulates adenylyl cyclase to convert ATP into cyclic adenosine monophosphate (cAMP). Elevated intracellular cAMP activates protein kinase A (PKA), initiating a phosphorylation cascade with two primary metabolic outcomes. First, PKA phosphorylates phosphorylase kinase, converting it from its inactive (b) form to its active (a) form. Active phosphorylase kinase then phosphorylates glycogen phosphorylase, which catalyzes the sequential cleavage of glucose-1-phosphate units from glycogen. This process — glycogenolysis — rapidly mobilizes hepatic glucose stores. Simultaneously, PKA phosphorylates and inactivates glycogen synthase, preventing further glycogen formation. Second, glucagon-mediated PKA activity stimulates hepatic gluconeogenesis by phosphorylating the transcription factor CREB (cAMP response element-binding protein), which upregulates expression of key gluconeogenic enzymes including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). PKA also inhibits glycolysis by reducing activity of pyruvate kinase and phosphofructokinase-2. The combined effect is a rapid and sustained elevation of blood glucose, typically raising levels by 30-100 mg/dL within 10-20 minutes of parenteral administration.
What to Expect
Glucagon absorbed from injection or nasal mucosa; hepatic signaling cascade initiated
Blood glucose begins to rise as glycogenolysis mobilizes hepatic glucose stores
Most patients regain consciousness; blood glucose typically elevated 30-100 mg/dL above baseline
Peak plasma glucose reached; patient should be given oral carbohydrates to sustain recovery
Glucagon effect waning; risk of rebound hypoglycemia if glycogen stores are depleted
Dosing Protocol
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 0.5mg | Single dose |
| Moderate | 1mg | Single dose |
| Aggressive | 1mg | Single dose |
Note: Glucagon is an FDA-approved emergency treatment for severe hypoglycemia in people with diabetes. It is a 29-amino-acid peptide hormone produced by alpha cells of the pancreatic islets of Langerhans. Unlike most peptides used in research or optimization contexts, glucagon is strictly an emergency rescue medication. It is available as a lyophilized powder for reconstitution (GlucaGen, Glucagon Emergency Kit), a ready-to-use liquid autoinjector (Gvoke), and an intranasal dry powder (Baqsimi). Each formulation is designed for rapid deployment during hypoglycemic emergencies when the patient is unable to consume oral carbohydrates. Reconstituted glucagon should be used immediately and never stored for later use. The 1 mg dose is standard for adults and children over 25 kg; a 0.5 mg dose is recommended for pediatric patients under 25 kg.
How to Inject Glucagon (GlucaGen)
For the GlucaGen or Glucagon Emergency Kit: remove the flip-off seal from the vial of lyophilized glucagon and inject the entire contents of the accompanying diluent syringe into the vial. Swirl gently until the powder is completely dissolved, producing a clear, colorless solution. Do not use if the solution is cloudy or contains particles. For adults and children over 25 kg, administer the full 1 mg (1 mL) dose via subcutaneous or intramuscular injection into the upper arm, thigh, or buttock. For children under 25 kg, administer 0.5 mg (0.5 mL). For Baqsimi intranasal powder: insert the device tip into one nostril and press the plunger firmly to deliver the full 3 mg dose — no inhalation required. For Gvoke autoinjector or prefilled syringe: inject 0.5 mg or 1 mg subcutaneously per weight-based dosing. After administration, position the patient on their side to prevent aspiration if vomiting occurs. Once the patient regains consciousness, provide oral carbohydrates to prevent relapse.
Cycling Protocol
Emergency use only — glucagon is not cycled. Administered as a single rescue dose during episodes of severe hypoglycemia. No ongoing or prophylactic dosing protocol exists.
Pharmacokinetics
Source: Cersosimo et al., Diabetes Care 1985; PMID 3971846 — IV t½ 8-18 min; IM ~26 min; SC/IN ~35-45 min
Loading the interactive decay curve.
Side Effects
Nausea is the most common adverse effect of glucagon, reported in up to 35% of patients. Vomiting frequently accompanies nausea, particularly with rapid intravenous injection of doses exceeding 1 mg. Headache is another commonly reported side effect. Transient increases in blood pressure and heart rate may occur, especially in patients concurrently taking beta-blockers. Intranasal administration (Baqsimi) may also cause watery eyes, nasal congestion, nasal itching, and upper respiratory tract irritation. Injection site reactions including redness and swelling have been reported with subcutaneous and intramuscular formulations. Rare but serious adverse reactions include generalized allergic reactions, anaphylactic shock with hypotension and breathing difficulties, and rebound hypoglycemia — particularly in patients with depleted hepatic glycogen stores from prolonged fasting, adrenal insufficiency, or chronic hypoglycemia. Hypokalemia has been observed in overdose situations.
Contraindications
- Known pheochromocytoma — glucagon may stimulate catecholamine release causing hypertensive crisis
- Known insulinoma — may cause paradoxical hypoglycemia via stimulated insulin release
- Known glucagonoma — risk of exaggerated hyperglycemic response
- Hypersensitivity to glucagon or any excipient (including lactose monohydrate in some formulations)
- Pregnancy — FDA Category B; no adequate human studies; use only if clearly needed
- Breastfeeding — unknown whether glucagon is excreted in human milk; use with caution
Drug Interactions
- Insulin — directly antagonizes glucagon effects on blood glucose
- Beta-blockers — may cause exaggerated transient increases in blood pressure and heart rate
- Indomethacin — may blunt or abolish the hyperglycemic effect of glucagon
- Warfarin — glucagon may potentiate the anticoagulant effect, increasing bleeding risk
Storage & Stability
Molecular Profile
Related Peptides
References
- GlucaGen (glucagon) for injection — FDA Prescribing InformationFDA Label
- BAQSIMI (glucagon) nasal powder — FDA Prescribing InformationFDA Label
- Pharmacokinetics and Bioavailability of Injected Glucagon: Differences Between Intramuscular, Subcutaneous, and Intravenous AdministrationPubMed 3971846
- Treatment of severe diabetic hypoglycemia with glucagon: an underutilized therapeutic approachPubMed 21969805