What is Glucagon and How Does It Work?|When and How To Inject Glucagon?

People with type 1 diabetes are familiar with the condition of hypoglycemia, or low blood sugar. It is essential to recognize the signs and symptoms of hypoglycemia because if left untreated, hypoglycemia can lead to a life-threatening situation. A state of confusion, profuse sweating, dizziness, and sudden onset of extreme hunger are some of the warning signs that your blood sugar levels are going down. While most of the time, it is possible to treat low blood sugar yourself by consuming fast-acting carbohydrates, sometimes low blood sugar can become a medical emergency, especially if it is not treated promptly. In cases of severe hypoglycemia, you may need to use a medication known as glucagon. But can glucagon treat hypoglycemia? Here’s everything you need to know about using glucagon for treating hypoglycemia.

What is Glucagon and How Does It Work?

Glucagon is a hormone that is naturally produced by alpha cells present in your pancreas, known as the islets of Langerhans.(1) Glucagon has a critical role to play in the body as it allows the body to regulate the utilization of fats and glucose. Your liver stores the excess glucose in your body in case the blood sugar goes down.(2,3) The body and brain depend on this glucose for producing energy, which is why it is important that this energy source should be made available to the body fast. In a person with diabetes, natural glucagon does not work correctly, and glucagon medication can help trigger the liver to release the stored glucose in the liver. Once the stored glucose is released from the liver, it causes blood sugar levels to increase quickly.(4,5)

In normal circumstances, glucagon gets released by the body when the blood glucose levels go down. It is also released in situations where the body needs extra glucose, such as when you are exercising.(6)

Natural glucagon is released to perform the following tasks in the body:(7)

  • Activating the process of gluconeogenesis, which involves the conversion of amino acids into glucose.
  • Stimulating the liver to break down glycogen to release it into the bloodstream in the form of glucose.
  • Breaking down of the stored fat or triglycerides in the body into fatty acids to be used as fuel by the cells.

However, in people with diabetes, glucagon is not able to function properly. If you have type 1 diabetes, your doctor is going to recommend that you buy an emergency glucagon kit in case you experience an episode of severe low blood sugar. In cases of severe hypoglycemia, you may need someone to administer the glucagon to you.(8)

Connection of Glucagon and Insulin

In a person with diabetes, the hormones glucagon and insulin have a close connection. The two hormones work together to closely regulate the blood sugar levels. While insulin works to lower the blood sugar levels, glucagon triggers the liver to release the stored glucose to increase the blood sugar levels. In a person without diabetes, when the blood sugar levels drop, the insulin release also stops at the same time.

However, in a person with type 1 diabetes, the insulin-producing cells in the body are damaged, which is why they need to take insulin on a daily basis. They need to either use an insulin pump or inject insulin every day. Another challenge that people with type 1 diabetes face is that within five years of being diagnosed with the condition, low blood sugar can end up not triggering the release of sufficient glucagon to increase the blood sugar levels back to a normal range.(9)

This is why, in cases of severe hypoglycemia, glucagon is used as a medication to increase the blood sugar levels. In severe hypoglycemia, a person is usually incapable of administering the glucagon themselves and may need someone else to give them the medication. Glucagon medication will trigger the release of glucose from the liver that will increase the levels of blood sugar, just as the natural hormone is supposed to do.(10)

Types of Glucagon Medication for Diabetes

At present, the US Food and Drug Administration (FDA) has approved two types of injectable glucagon emergency medication for treating severe hypoglycemia.(11) These include:

  1. GlucaGen HypoKit
  2. Glucagon Emergency Kit

These medications are only available by prescription. More recently, in July 2019, the FDA also approved a glucagon nasal powder.(12) Known as Baqsimi, this medication is the only form of glucagon available for treating severe hypoglycemia that does not need to be injected. You can only get Baqsimi on a prescription.(13)

If you have a glucagon medication kit, you must keep checking the expiration date regularly as the medication is good to be used for 24 months from the date of manufacturing. Glucagon medication must be stored away from direct sunlight and at room temperature.

When and How To Inject Glucagon?

When you have type 1 diabetes and have an episode of severe hypoglycemia, you may not be able to treat yourself when you need glucagon. Glucagon medication may need to be used when a person with type 1 diabetes is:

  • Unconscious
  • Not responsive
  • Refusing to swallow or drink a source of fast-acting carbohydrate or sugar by mouth.

In any of the above situations, one should never try to force a person to swallow any food or make them drink a source of sugar because there is a chance of the person choking. If you are unsure whether glucagon should be used or not, it is essential to understand that it is almost impossible for anybody to overdose on glucagon.(14) This is why if you are unsure about whether to give glucagon or not, it is always better to administer it rather than leaving the person untreated.

In cases of a severe hypoglycemic episode, it is best to immediately call for medical assistance or your local emergency number like 911.

For treating severe hypoglycemia with a glucagon kit, here are the steps you need to follow:

  • Open the glucagon medical kit. There will be a syringe filled with sterile saline liquid inside and a small bottle of powder.
  • Take the bottle of powder and remove the cap.
  • Remove the protective cap on the needle of the syringe and push the needle all the way inside the bottle.
  • Push the entire saline liquid from the syringe into the powder bottle.
  • Now gently swirl the bottle to dissolve the glucagon powder. The liquid should appear clear once it has been mixed properly.
  • Read the dosage instructions given on the kit to draw the required amount of glucagon mixture into the syringe.
  • Inject the glucagon into the person’s upper arm, outer thigh, or buttock. It is okay to inject the glucagon through the fabric.

Now roll the person to their side and position their top knee at an angle – it should look like they are running. This stabilizes them and is known as the ‘recovery position.’

You should never try to administer glucagon to a person by mouth as the process will not work.

What is the Right Dose of Glucagon?

For either type of injectable glucagon, the dosing is as follows:(15)

  • 1 mL of glucagon solution for children six years and above, and also for adults.
  • 0.5 mL of glucagon solution for children who are five years and younger, or for children who weigh less than 44 lbs.
  • If you are using the glucagon nasal powder, it is only available in a single-use dosage of 3 milligrams.(16)

Are there any Side Effects of Using Glucagon?

There are usually minor side effects of using glucagon. Some people have reported experiencing nausea and vomiting after being given injectable glucagon.(17)

However, it is essential to keep in mind that nausea and vomiting are also two of the common symptoms of severe hypoglycemia. This makes it difficult to determine whether a person is experiencing a symptom of severe hypoglycemia or a side effect of the glucagon.

Apart from nausea and vomiting, the FDA has said that nasal glucagon may also cause the following side effects:(18)

It is important to seek immediate medical assistance if you find that nausea and vomiting prevent a person from eating or drinking after they have been administered glucagon.

What Happens After Receiving Glucagon?

After receiving glucagon, a person should wake up within 15 to 20 minutes. If a person does not wake up after 20 minutes, you should call for medical assistance, or you can also give them another dose of glucagon.

After a person wakes up, they should do the following:

  • Check their blood sugar levels.
  • Have at least 15 grams of any quick-acting carbohydrate, including fruit juice or soda that contains sugar and can be safely swallowed.
  • Have a small snack like a granola bar or milk, cheese and crackers, or a peanut butter sandwich. They can also have a full meal within the hour of waking up.
  • They also need to check their blood sugar levels once every hour for at least the next four to five hours.

Anyone with severe low blood sugar that needs to be treated with glucagon should inform their doctor about the episode. It is also important to replace your emergency glucagon kit right away since the present one has been used.

Conclusion

If you treat low blood sugar immediately, most of the time, it won’t drop low enough to need treatment with glucagon. It will also prevent your condition from deteriorating into severe hypoglycemia. Glucagon is only required when a person develops severe hypoglycemia and is no longer in a condition to treat themselves.

In most cases, though, a person with diabetes is able to treat low blood sugar on their own without the need for glucagon. The best treatment for low blood sugar is to consume at least 15 grams of fast-acting sugar such as glucose tablets, soda or fruit juice, or even a tablespoon of honey, sugar, or corn syrup.

Many cases of hypoglycemia can be easily managed, but it is always important that you remain prepared. Severe hypoglycemia may develop without your realizing, and you may need to be treated with glucagon. It is a good idea to wear a medical ID bracelet that lets other people know you have type 1 diabetes and the location of your glucagon treatment.

Informing others about how to use your glucagon medication and where you keep it can help you feel more in control and more comfortable in the long run. To avoid such incidences, it is best to learn how to manage your diabetes and keep your blood sugar levels under control.

References:

  1. Unger, R.H., 1971. Glucagon physiology and pathophysiology. New England Journal of Medicine, 285(8), pp.443-449.
  2. Jiang, G. and Zhang, B.B., 2003. Glucagon and regulation of glucose metabolism. American Journal of Physiology-Endocrinology And Metabolism, 284(4), pp.E671-E678.
  3. Drucker, D.J., 2001. Minireview: the glucagon-like peptides. Endocrinology, 142(2), pp.521-527.
  4. Cryer, P.E., Davis, S.N. and Shamoon, H., 2003. Hypoglycemia in diabetes. Diabetes care, 26(6), pp.1902-1912.
  5. Cryer, P.E., Fisher, J.N. and Shamoon, H., 1994. Hypoglycemia. Diabetes care, 17(7), pp.734-755.
  6. Ahlborg, G.U.N.V.O.R. and Felig, P.H.I.L.I.P., 1976. Influence of glucose ingestion on fuel-hormone response during prolonged exercise. Journal of Applied Physiology, 41(5), pp.683-688.
  7. Assan, R., Attali, J.R., Ballerio, G., Boillot, J. and Girard, J.R., 1977. Glucagon secretion induced by natural and artificial amino acids in the perfused rat pancreas. Diabetes, 26(4), pp.300-307.
  8. Cryer, P.E., 2012. Minireview: Glucagon in the pathogenesis of hypoglycemia and hyperglycemia in diabetes. Endocrinology, 153(3), pp.1039-1048.
  9. McCrimmon, R.J. and Sherwin, R.S., 2010. Hypoglycemia in type 1 diabetes. Diabetes, 59(10), pp.2333-2339.
  10. Siafarikas, A., Johnston, R.J., Bulsara, M.K., O’Leary, P., Jones, T.W. and Davis, E.A., 2012. Early loss of the glucagon response to hypoglycemia in adolescents with type 1 diabetes. Diabetes Care, 35(8), pp.1757-1762.
  11. Accessdata.fda.gov. 2020. [online] Available at: <https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/020928s055lbl.pdf> [Accessed 18 November 2020].
  12. U.S. Food and Drug Administration. 2020. FDA Approves First Treatment For Severe Hypoglycemia That Can Be Administered Without An Injection. [online] Available at: [Accessed 18 November 2020].
  13. Elliott, W. and Chan, J., 2019. Glucagon Nasal Powder (Baqsimi). Internal Medicine Alert, 41(16).
  14. Diabetesatschool.ca. 2020. Glucagon: What It Is, And How To Use It | Diabetes At School. [online] Available at: <https://www.diabetesatschool.ca/schools/glucagon> [Accessed 18 November 2020].
  15. Wilson, L.M. and Castle, J.R., 2018. Stable liquid glucagon: beyond emergency hypoglycemia rescue. Journal of diabetes science and technology, 12(4), pp.847-853.
  16. Investor.lilly.com. 2020. [online] Available at: <https://investor.lilly.com/node/41601/pdf> [Accessed 18 November 2020].
  17. Pontiroli, A.E. and Tagliabue, E., 2020. Intranasal versus injectable glucagon for hypoglycemia in type 1 diabetes: systematic review and meta-analysis. Acta Diabetologica, pp.1-7.
  18. Rosenfalck, A.M., Bendtson, I., Jørgensen, S. and Binder, C., 1992. Nasal glucagon in the treatment of hypoglycaemia in type 1 (insulin-dependent) diabetic patients. Diabetes research and clinical practice, 17(1), pp.43-50.

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