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Severe Hypoglycemia: Your FAQs Answered

  • Authors: Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES
  • CE Released: 11/15/2021
  • Valid for credit through: 11/15/2022
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Target Audience and Goal Statement

This activity is intended for pharmacists.

The goal of this activity is to improve pharmacists' ability to discuss and educate patients on treatment options for severe hypoglycemia.

Upon completion of this activity, participants will:

  • Have increased knowledge regarding the
    • Clinical differences in therapeutic options for treating severe hypoglycemia
    • Identification of patients at risk of severe hypoglycemia
    • Patient education clinical pearls related to treatment strategies for severe hypoglycemia


As an organization accredited by the ACCME, Medscape, LLC requires everyone who is in a position to control the content of an education activity to disclose all relevant financial relationships with any commercial interest. The ACCME defines "relevant financial relationships" as financial relationships in any amount, occurring within the past 12 months, including financial relationships of a spouse or life partner, that could create a conflict of interest.

Medscape, LLC encourages Authors to identify investigational products or off-label uses of products regulated by the US Food and Drug Administration, at first mention and where appropriate in the content.

All of the relevant financial relationships listed for these individuals have been mitigated.


  • Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES

    Endocrine Clinical Pharmacy Specialist
    CGM and Remote Monitoring Program Coordinator
    Cleveland Clinic Endocrinology & Metabolism Institute Diabetes Center
    Cleveland, Ohio


    Disclosure: Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES, has the following relevant financial relationships:
    Advisor or consultant for: Diatribe; Lilly; Sanofi; Undermyfork
    Speaker or a member of a speakers bureau for: Abbott; Bayer; Dexcom; Insulet; Medtronic; Novo Nordisk; Xeris Pharmaceuticals


  • Anne G. Le, PharmD

    Senior Medical Education Director, Medscape, LLC


    Disclosure: Anne G. Le, PharmD, has disclosed no relevant financial relationships.

  • Kim Storck, PharmD, RPh

    Senior Director, Medical Writing, Medscape, LLC


    Disclosure: Kim Storck, PharmD, RPh, has disclosed no relevant financial relationships.

CE Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC


    Disclosure: Amanda Jett, PharmD, BCACP, has disclosed no relevant financial relationships.

None of the nonfaculty planners for this educational activity have relevant financial relationship(s) to disclose with ineligible companies whose primary business is producing, marketing, selling, reselling, or distributing healthcare products used by or on patients.

Peer Reviewer

This activity has been peer reviewed and the reviewer has disclosed no relevant financial relationships.

Accreditation Statements

In support of improving patient care, Medscape, LLC is jointly accredited by the Accreditation Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE), and the American Nurses Credentialing Center (ANCC), to provide continuing education for the healthcare team.

    For Pharmacists

  • Medscape designates this continuing education activity for 0.25 contact hour(s) (0.025 CEUs) (Universal Activity Number: JA0007105-0000-21-576-H01-P).

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Severe Hypoglycemia: Your FAQs Answered

Authors: Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCESFaculty and Disclosures

CE Released: 11/15/2021

Valid for credit through: 11/15/2022


Medscape recently sat with diabetes expert and advocate Diana Isaacs, PharmD, to answer your frequently asked questions about severe hypoglycemia. Dr Isaacs is a clinical pharmacy specialist at Cleveland Clinic Endocrinology & Metabolism Institute Diabetes Center and past recipient of the prestigious ADCES Diabetes Care and Education Specialist of the Year Award.

Medscape: How often and when should I discuss a hypoglycemia action plan with my patients who have diabetes?

Diana Isaacs, PharmD, BCPS, BCACP, BC-ADM, CDCES: According to the American Diabetes Association (ADA) Standards of Care, hypoglycemic risk and occurrence of hypoglycemia should be reviewed at every visit, regardless of the patient's duration of diabetes.[1] Ask your patients with diabetes if they've had a recent hypoglycemic event and confirm that they have an action plan in place.

Medscape: Which patients are at the highest risk for hypoglycemia?

Dr Isaacs: In general, this would include all patients with type 1 diabetes (T1D), insulin-requiring patients with type 2 diabetes (T2D), and patients taking sulfonylureas (SUs).[1,2] Any patient with reduced ability to recognize hypoglycemic symptoms and effectively communicate their needs is also at high risk.[1]

Medscape: How does the ADA define severe hypoglycemia?

Dr Isaacs: The ADA divides hypoglycemia into 3 different levels. Level 1 and level 2 hypoglycemia are defined by numeric thresholds; level 2 is a blood glucose (BG) < 54 mg/dL (3.0 mmol/L), and level 1 is BG ≥ 54 mg/dL and < 70 mg/dL (< 3.9 mmol/L). Level 3, severe hypoglycemia, is defined as an event requiring assistance from someone else to treat the hypoglycemic episode.[1] In a conscious person, first-line treatment is to take 15 grams of glucose[2] in the form of glucose tablets, hard candy, juice, or soda, whereas a patient with severe hypoglycemia may have hypoglycemic unawareness or could be unconscious, and therefore assistance from someone else to treat the episode is necessary.

Medscape: Who should be prescribed glucagon to treat hypoglycemia?

Dr Isaacs: Anyone at increased risk for level 2 or 3 hypoglycemia should be prescribed glucagon so that it is available if needed.[1] As previously mentioned, this includes all patients with T1D, insulin-requiring patients with T2D, and patients taking SUs.[2]

Medscape: What formulations of glucagon are available for the treatment of severe hypoglycemia?

Dr Isaacs: Until recently the only glucagon option was the glucagon emergency kit. Although effective, this formulation requires reconstitution before injection, posing a barrier to quick administration in emergencies.[2] Now multiple user-friendly formulations of glucagon are available that do not require reconstitution. Two injectable products -- stable liquid glucagon and dasiglucagon -- are available as either a ready-to-use prefilled syringe or an autoinjector. There is also nasal glucagon, which is a dry powder administered directly into a person's nose. Because the new options do not require reconstitution, they are easier to administer than the emergency kit.[2]

Medscape: In your experience, are prescribers of the glucagon emergency kit aware of the newer formulations?

Dr Isaacs: I find prescribers are either not familiar with the newer glucagon formulations or, if they're aware, they assume that the newer formulations won't be covered by insurance. Pharmacists can proactively inform the provider of a patient's coverage or initiate a prior authorization. Although it takes some extra steps, it is worth it to overcome administration barriers.

Medscape: Are there notable differences between the formulations other than their mode of administration?

Dr Isaacs: Yes. Pharmacists need to be aware of the specific ages for use and doses of each glucagon formulation (Table 1). Nasal glucagon is available in a 3.0-mg dose for use in patients 4 years and older.[3] Stable liquid glucagon is available in 0.5-mg and 1.0-mg doses. Dosing is weight- and age- dependent; 0.5 mg is indicated from 2 years old to < 12 years old and < 45 kg; and 1.0 mg is indicated for 12 years and older or if over 45 kg.[4] Dasiglucagon is available in a 0.6-mg dose and can be used in patients 6 years and older.[5]

Table 1. Glucagon Rescue Medications for Diabetes-Related Hypoglycemia [3-6]



Dose Range





Pediatric (Age/
Weight Dosing)


Injection requiring mixing of glucagon powder[6]

1.0-mg/1-mL vial + syringe

1 mg

< 6 years or < 25 kg: 0.5 mg

≥ 6 years or > 25 kg: 1.0 mg

All ages approved

SC or IM administration

Nasal glucagon powder[3]

3.0-mg intranasal device

3 mg

< 4 years: not recommended

≥ 4 years: 3.0 mg

Approved age ≥ 4 years

Nasal administration

Injectable liquid stable glucagon[4]

0.5-mg/1.0-mg prefilled syringe or 0.5-mg/1.0-mg autoinjector

1 mg

< 2 years: not recommended

2 years to 12 years: < 45 kg: 0.5 mg or ≥ 45 kg: 1.0 mg

≥ 12 years: 1.0 mg

Approved ≥ 2 years

SC administration in arm, thigh, abdomen


Injectable liquid stable glucagon analogue (dasiglucagon)[5]

0.6 mg/0.6 mL prefilled syringe autoinjector

0.6 mg

< 6 years: not recommended

≥ 6 years: 0.6 mg

Approved ≥ 6 years

SC administration in
lower abdomen, buttocks, thigh, outer upper arm


IM, intramuscular; SC, subcutaneous.

Medscape: How should I counsel patients on the nasal administration of glucagon?

Dr Isaacs: I recommend using a demonstration device; this is a great way to physically show patients how to administer the drug and allow them to practice. Demonstration devices can be requested through the product manufacturer. Nasal glucagon is removed from the package and inserted into the person's nose. One actuation into 1 nostril delivers the recommended dose (Table 2). The dose does not need to be inhaled to be effective, and nasal congestion does not affect its absorption.[3,7]

Table 2. Steps to Administer Nasal Glucagon Adapted From the Product Package Insert[2]




Remove the shrink wrap on the outside of the yellow tube by pulling on the red stripe.


Open the lid and remove the device from the tube. Caution: Do not press the plunger until ready to give the dose.


Hold device between fingers and thumb.


Insert tip gently into 1 nostril until finger(s) touch the outside of the nose.


Push plunger firmly with the thumb. Dose is complete when the green line disappears. One actuation into 1 nostril delivers the recommended dose.

With all glucagon formulations, if the person is still unalert, disoriented, or their BG has not increased to > 70 mg/dL in the 15 minutes after the first dose, another dose of glucagon can be administered.[2] It is encouraged that patients have at least 2 doses of glucagon on hand. All options are available in a double pack for this purpose. Any glucagon formulation can cause nausea and vomiting, so the person must be rolled onto their side to keep the airway open and avoid aspiration.[2]

Medscape: How should I counsel patients on glucagon injections?

Dr Isaacs: Demonstrate (when possible) how to administer the type of glucagon the patient is prescribed. Choose an injection site (ie, lower abdomen, outer thigh, or outer arm) and expose the skin. If using a prefilled syringe, dasiglucagon is inserted into the skin at a 45-degree angle.[5] Stable liquid glucagon is inserted at a 90-degree angle.[2] Once the syringe is inserted, push the plunger to administer the dose (Table 3). If using an autoinjector pen, the pen is placed directly onto the skin (not inserted) before pushing the plunger. The plunger is held for 5 to 10 seconds until the dose is fully administered (Table 4).[2]

Table 3. Steps to Administer Glucagon Prefilled Syringes Adapted From the Product Package Inserts[2]


Liquid Stable Glucagon

Liquid Stable Glucagon Analogue (Dasiglucagon)


Tear open pouch at dotted line, remove syringe.

Hold the red protective case upright with the gray cap on top. Pull the gray cap up to open.


Choose injection site (lower abdomen, outer thigh, or outer arm) and expose the skin.

Choose injection site (lower abdomen, outer thigh, or outer arm) and expose the skin.


Pull off needle cap. Do not remove air bubbles. To help prevent accidental needle sticks, do not put your thumb, fingers, or hand on or near the needle.

Pull the gray needle cover straight off. Be careful not to bend the needle.


Pinch the skin; insert the needle at 90-degree angle. Push the plunger.

Pinch the skin and insert the entire needle into the skin at a 45-degree angle. Release the pinched skin and slowly press the plunger rod all the way down until the syringe is empty and the plunger rod stops.


Remove the needle.

Remove the needle.

Table 4. Steps to Administer Glucagon Autoinjector (Pens) Adapted From the Product Package Inserts[2]


Liquid Stable Glucagon

Liquid Stable Glucagon Analogue (Dasiglucagon)


Tear open pouch at dotted line, remove pen device.

Hold the red protective case upright and remove gray lid. Carefully remove pen from protective case without dropping it.


Pull off the red needle cap straight off the device. Do not put your thumb, fingers, or hand on or near the needle guard.

Pull the gray cap straight off.


Choose injection site (lower abdomen, outer thigh, or outer arm); push and hold straight down against the injection site. Listen for a click.

Choose injection site (lower abdomen, outer thigh, or outer arm); push device straight down.


Continue to hold the device down and count slowly to 5. When the injection is complete, the viewing window will be red.

Keep holding down and slowly count to 10 seconds. The medicine window will turn red and you may hear a second click.


Lift the pen straight up from the injection site. The yellow needle guard will lock over the needle.

Remove by lifting the pen straight up. The yellow needle guard will cover the needle and lock, preventing an accidental stick injury.

Medscape: You'd mentioned that it is good to have 2 doses on hand. Do you find that insurance will cover 2 doses?

Dr Isaacs: Insurance will usually cover 2 doses or the double pack, but coverage does vary from product to product. Insurance coverage for the newer glucagon formulations has improved because there is evidence of their benefit compared with the emergency kit. For example, in the formative usability study, 88% of trained and untrained users successfully administered a rescue injection using the glucagon autoinjector pen vs 31% with a glucagon emergency kit (P < .05). Mean total rescue time was significantly quicker with the pen (48 seconds vs 109 seconds; P < .05).[8]

If an insurance plan only covers 1 dose at a time, ensure there are refills on the prescription, and encourage the patient to refill the product the following month. The pharmacist can also initiate an override or prior authorization with the insurance company. A benefit to having 2 doses on hand is the ability to administer a second dose, if needed, and keep glucagon in multiple places. For example, children may need to keep 1 at school and 1 at home.

Medscape: Can patients use expired glucagon?

Dr Isaacs: No. The shelf life for most glucagon is 2 years, and care should be taken to ensure glucagon is not expired.[1] When counseling patients about hypoglycemia, ask if they have glucagon on hand, know where it is and how to use it, and periodically check the expiration date. You don't want to risk that the therapy will be ineffective in an emergency if it is expired.

Medscape: What is the most common question about glucagon asked by patients and caregivers?

Dr Isaacs: That's the thing -- many patients haven't had conversations about glucagon. Our clinic recently put up a sign that said, "If you're on insulin, you should ask about glucagon." It was amazing how many people asked about it from the sign. Getting the word out about glucagon and the new formulations is important for patient safety. Educating patients about the different options and how they're used helps them make an informed and personalized choice.

Medscape: Can newer diabetes technology like continuous glucose monitoring (CGM) eradicate a patient's risk for hypoglycemia?

Dr Isaacs: CGM can reduce the risk of hypoglycemia, but it does not eradicate it, and severe hypoglycemia still occurs with CGM.[1] Anyone taking insulin is at risk for hypoglycemia. Even if a person follows all dietary and lifestyle recommendations, numerous unpredictable variables still affect hypoglycemic risk (ie, activity and stress levels). So, unfortunately, despite CGM and other technology, hypoglycemia is still a concern.

Medscape: Do you educate patients about CGM as a potential option if they're concerned about hypoglycemia?

Dr Isaacs: Yes, I make sure anyone taking insulin is aware of CGM and its benefits, particularly in reducing hypoglycemic risk.[1] CGM has been shown to reduce the risk of hypoglycemia in patients with diabetes on multiple daily insulin injections.[9-11] In addition, the ADA recommends CGM for patients with T2D on intensive insulin regimens to improve glucose control and decrease hypoglycemia.[11]

Medscape: Only 5% of glucagon prescriptions are filled after an emergency department visit for severe hypoglycemia.[12] What can pharmacists do to increase this percentage?

Dr Isaacs: Pharmacists are in a unique, influential position to improve awareness of newer glucagon formulations and facilitate their use. If the glucagon emergency kit is prescribed, a pharmacist can proactively reach out to the patient's healthcare provider and ask to switch the formulation to a newer option. In our clinic, we're trying to implement where pharmacists can automatically substitute glucagon formulations depending on patient preference and what is preferred by the insurance company. Patient counseling and reminder calls are also helpful to increase awareness. It only takes a few minutes to show a person how to use glucagon and make sure they feel comfortable. Taking those few extra minutes can save lives.