What to Know About GlucaGen (Glucagon)

GlucaGen (glucagon) is an injectable medication and naturally occurring hormone that causes the liver to convert stores of glycogen into glucose and release it into the bloodstream, increasing blood sugar levels. Glucagon is available as a prescription medication used primarily for emergencies to reverse low blood sugar (hypoglycemia) when other options are not available. It may be administered by trained caregivers at home, emergency responders, or health care providers.

Unlike sugar (glucose or dextrose), glucagon can be injected into the muscle directly, making it easy to use in an emergency. Glucagon is also used for certain diagnostic imaging and off-label to treat overdoses of two classes of cardiac medications: beta blockers and calcium channel blockers. Glucagon is part of a class of pharmaceuticals known as hormonal agents, which are natural or synthetic versions of hormones. It is a single-chain polypeptide consisting of 29 amino acids.

The US Food and Drug Administration (FDA) has approved glucagon for two uses: the emergency treatment of severe hypoglycemia and as a diagnostic aid in imaging studies (specifically CT and MRI) of the gastrointestinal (GI) tract.

Severe Hypoglycemia

Low blood sugar (hypoglycemia) is a potentially life-threatening medical emergency that is most commonly seen in patients with insulin-dependent diabetes mellitus. Patients with this condition control their blood sugar with a combination of injectable versions of insulin and diet. It is easy to accidentally force blood sugar too low, which results in emergency hypoglycemia. Generally, severe hypoglycemia is measured with a glucometer at 70 milligrams per deciliter (mg/dL) or 3.9 millimoles per liter (mmol/L) or below, associated with confusion or coma.

The preferred treatment for hypoglycemia is to increase the patient's blood sugar through the ingestion of carbohydrates. In other words, eat sugar. Hypoglycemia causes confusion and, in some severe cases, a loss of consciousness. If the patient is unable to eat something, only an injectable medication can help.

Emergency healthcare providers (paramedics, emergency nurses, and emergency physicians) have intravenous dextrose available as an emergency medicine for treating hypoglycemic patients. Dextrose is not available for patients or family members to administer without medical training.

Previously, only orally ingested glucose was available for patients and lay rescuers to administer without the aid of a health care provider. Oral glucose is simply a carbohydrate and almost any carbohydrate will do. Patients often respond well to things like frozen juice concentrate or other simple sugars as emergency treatments for mild hypoglycemia.

Glucagon was introduced as an emergency treatment to allow patients an injectable option to use at home. Glucagon triggers the conversion of glycogen stores in the liver into glucose and introduces the glucose into the bloodstream. It is only effective if the patient has sufficient glycogen stores in the liver and muscles prior to administration. If the patient does not have adequate glycogen stores, glucagon will not work properly.

Diagnostic Imaging

Glucagon is used in some imaging procedures along with magnetic resonance imaging (MRI) or computed tomography (CT) scans to observe gastric function. Glucagon relaxes the smooth muscle of the GI tract and temporarily halts gut motility to facilitate images.

Off-Label Uses

High doses of glucagon are often used to treat beta blocker and calcium channel blocker overdoses. The effects of glucagon are well documented if not completely understood. Glucagon improves heart rate and blood pressure in patients that have taken too many beta blockers or calcium channel blockers.

Glucagon is short-acting in these instances and may need to be administered as an infusion (intravenous drip) in order to sustain any substantial change in cardiac output.

Glucagon is available primarily as an emergency medication for use during severe episodes of hypoglycemia. A glucagon emergency kit and training to use it may be given to caregivers of patients at risk for severe hypoglycemia.

Precautions and Contraindications

There are no obvious precautions or contraindications of administering glucagon as an emergency medication during periods of severe hypoglycemia where the patient is unable to communicate. Glucagon is only effective in patients that have glycogen stores remaining in the liver and muscles. If the patient's glycogen stores have already been depleted, glucagon is ineffective.

Patients with a history of pheochromocytoma (adrenal gland tumor) could have a severe high blood pressure (hypertensive) reaction to the administration of glucagon. Glucagon is contraindicated in patients with known pheochromocytoma. Also, patients with a history of insulinoma or glucagonoma (tumors of the pancreas) could have secondary hypoglycemia from the use of glucagon. These patients should not receive the emergency kit form of glucagon for use in an emergency setting. However, in a medical emergency, the patient is often unable to relay such history to healthcare providers and glucagon may be administered as part of a standing protocol for the treatment of severe hypoglycemia.

Patients may be allergic to glucagon and develop an anaphylactic reaction to the medication. known allergies to glucagon are a contraindication for use.

Other Hormonal Agents

Insulin is the most commonly used hormonal agent and is also a hormone that is naturally secreted by the pancreas for control of blood sugar. Generally, insulin acts in the opposite manner to glucagon and lowers blood sugar. Glucagon increases it.

Epinephrine, norepinephrine, and dopamine are other examples of hormonal agents. All are used in emergency settings to treat various metabolic and cardiac conditions.

Glucagon is supplied as a powder and must be reconstituted (mixed with sterile water for injection) prior to administration. Initial adult dosage for emergency hypoglycemia is 1 milligram (mg) administered intravenously (IV), intramuscularly (IM), or subcutaneously (SQ).

Initial doses can be repeated once if no effect after five minutes. Further repeated doses for hypoglycemia are likely to be ineffective and other emergency treatment, usually intravenous dextrose, should be attempted.

Modifications

Children under 25 kilograms (kg) may receive 0.5 mg IV, IM, or SQ for severe hypoglycemia. This dose may be repeated once.

How to Take and Store

Glucagon is supplied in 1-mg vials as a powder that has to be reconstituted with sterile water for injection. In emergency kit form, glucagon is supplied with a second vial containing the sterile water. The sterile water is introduced into the vial containing the glucagon powder and the mixture is agitated (gently shaken) to create an injectable solution. The solution is then drawn up in a syringe for injection.

Once glucagon has been administered and the patient's level of consciousness increases, the patient should eat some form of complex carbohydrate to sustain blood sugar levels. Peanut butter is often a good choice if the patient does not have a peanut allergy. Without eating, the effects of glucagon are temporary and the patient is likely to return to a state of hypoglycemia quickly.

Glucagon causes slowing of gut motility, which just means it slows or stops the churning that happens in the esophagus, stomach, and intestines. It's the reason glucagon is used for imaging of the GI tract (saying, "hold still for the camera" doesn't work on your tummy), but it can lead to gastrointestinal upset.

Common

Nausea is the most common adverse effect of glucagon and it does sometimes lead to vomiting. For patients who receive glucagon as part of an imaging test, it could result in low blood sugar (hypoglycemia).

Severe

Rare side effects of glucagon include:

• Necrolytic migratory erythema (NME), a rash typically associated with a specific type of pancreatic cancer called a glucagonoma. Continuous infusions of glucagon over time can cause the rash (but it is not causing cancer).
• Allergic reactions
• Anxiety
• Abdominal pain
• Changes in heart rate or blood pressure, particularly causing a rapid heartbeat.

The most clinically significant interaction between glucagon and another medication is with Indacin (indomethacin), which is used to treat some headache disorders. Indomethacin can block the effects of glucagon on blood sugar, which would affect its usefulness in an emergency. Although rare and not well understood, glucagon could also increase bleeding in patients on blood thinners, particularly warfarin or Coumadin. Talk to your doctor if you are taking a blood thinner.