Preventing and Managing Hypoglycemia in Patients with Diabetes

Full update November 2019

Hypoglycemia is a serious concern in patients with diabetes. Hypoglycemia can cause irreversible cognitive impairment, dementia, falls, vehicular accidents, other injuries, and death.1 The table below addresses common clinical questions about hypoglycemia in patients with diabetes. Educate patients with our patient handout, How To Handle Low Blood Sugar.

Abbreviations: ADA = American Diabetes Association; IM = intramuscular; SC = subcutaneous

Clinical Question

Suggested Approach or Resource

Which patients are at highest risk of hypoglycemiaa?

Patients with Type 1 diabetes (highest risk)

  • Risk factors for severe hypoglycemiaa include prior episode of severe hypoglycemia, A1C <6%, hypoglycemic unawareness, long duration of diabetes, autonomic neuropathy, younger age (i.e., too young to recognize and self-treat mild hypoglycemia, or adolescent),intensive glycemic control14

Patients with type 2 diabetes using insulin or sulfonylurea (lower risk), especially with:

  • severe cognitive impairment, older age, low health literacy, food insecurity, poor glycemic control, hypoglycemic unawareness, long duration of insulin therapy, chronic kidney disease, or neuropathy,2 intensive glycemic control,14 bariatric surgery

Certain medications may affect perception or response to hypoglycemia:7

  • Beta-blockers, especially noncardioselective agents: may blunt adrenergic symptoms (e.g., anxiety, palpitations, sweating, shaking) and impair counterregulatory response.7 Patients can still feel faint, dizzy, confused, sleepy, weak or irritable, or have problems with speech or vision.2,7 They might also have a headache.2
  • SSRIs (may alter perception of hypoglycemic symptoms)

What are the symptoms of hypoglycemia?

Symptoms can be classified as autonomic (neurogenic) or neuroglycopenic.2

  • Autonomic: shakiness, tachycardia, sweating, anxiety, hunger, nausea, tingling
  • Neuroglycopenic: difficulty concentrating or speaking, confusion, weakness, dizziness, drowsiness, headache, vision changes

Do analog insulins pose a lower risk of hypoglycemia?

See our chart, Insulin Analogs vs Human Insulin.

What resources are available to help educate patients about hypoglycemia?

From the American Diabetes Association:

From Diabetes Canada:

How can hypoglycemia be prevented?

Patients should be educated to manage situations that put them at risk of hypoglycemia: fasting, delayed meals, alcohol use, exercise, or sleep.For example:

  • Patients should be educated about adjusting insulin use and carbohydrate intake for exercise.1
  • Patients on intensive insulin should periodically check nighttime fingersticks at a time corresponding to peak overnight insulin effect, to identify need for regimen change.2

In at-risk patients, ask about hypoglycemia at each visit.1

Choose a preprandial glucose target that balances glycemic control and risk of hypoglycemia: 80 to 130 mg/dL (4.4 to 7.2 mmol/L) [Evidence level B-3].1,3

Re-think the treatment regimen if the patient experiences hypoglycemia unawareness or level 3 hypoglycemia.a,1

For insulin-treated patients with hypoglycemia unawareness, or an episode of level 2 hypoglycemia,a target glucose should be increased to avoid hypoglycemia for several weeks to three months to help restore awareness.1,2

Prescribers, the patient, and caregivers should monitor cognitive function.1

Consider continuous glucose monitoring for appropriate patients.

Be watchful for medications that might cause hypoglycemia (e.g., quinolones, tramadol).15,16

What is the general approach to treatment of hypoglycemia?

If the patient is conscious, give glucose 15 to 20 g (20 g if severea) if blood glucose <70 mg/dL (4 mmol/L).1,2 See footnote b for glucose source examples. Repeat glucose 15 g in 15 minutes if blood glucose still <70 mg/dL (4 mmol/L).1.2

If the patient is unconscious, or unwilling to cooperate with oral intake, give glucagon.1,2 If intravenous access is available, give 20 to 50 mL of D50W (i.e., 10 to 25 g of glucose) over one to three minutes.2

  • It may take five to 15 minutes for the patient to regain consciousness after glucagon administration.4 Turn the patient on their side; they may vomit.4.6 Call 911.8,9 Glucagon may be repeated while waiting for emergency help.8

Once hypoglycemia is reversed, the patient should eat their usual meal, or snack if the usual mealtime is >1 hour away.2 The snack should consist of 15 g carbohydrate plus protein (e.g., seven crackers plus a piece of cheese, or a slice of bread plus two tablespoons of peanut butter).2,5

Patients taking acarbose (Precose [U.S.], Glucobay [Canada]) or miglitol (Glycet, Canada) must use glucose tablets, one cup of non-fat milk, or one tablespoon honey.2,13

Which patients should have a glucagon product on hand?

All patients at risk of level 2 hypoglycemiaa should have unexpired glucagon or dasiglucagon (U.S. only) on hand (Note:  dasiglucagon is NOT included in guideline recommendations, as it was FDA-approved approved after publication).1,22

  • The patient’s caregiver or frequent contacts (e.g., family, friends, school personnel, roommate, coworker, correctional officer) should be told where it is and how to use it.1,4,22

How should glucagon products be stored?


  • Keep Baqsimi in its shrink-wrapped tube to protect it from moisture.9,19
  • Avoid storing where the temperature may exceed 86oF (30oC).9,19 Baqsimi has a 24-month shelf-life from date of manufacture.21

GlucaGen Hypokit

  • U.S.: may be stored for up to 24 months (or up to expiration date, whichever is first) where temperature does not exceed 77oF (25oC).8 Protect from light by keeping in original packaging.8
  • Canada: store in refrigerator (2oC to 8oC). Patient may store up to 18 months (or up to expiration date, whichever is first), where temperature does not exceed 25oC.11 Keep from freezing.11 Keep in sealed packing. Protect from light.11

Gvoke HypoPen or Gvoke PFS (U.S.)

  • Store in sealed pouch at 68oC to 77oC.17 Gvoke shelf-life will be ≤24 months from date of manufacture.20

Zegalogue (U.S.)

  • Store in refrigerator (36°F to 46°F [2°C to 8°C]). May be stored for up to 12 months at room temperature between 68°F and 77°F (20°C and 25°C). Do not return Zegalogue to the refrigerator once it has been removed.22
  • Protect from light by keeping in original packaging.22

How do newer glucagon products compare to traditional glucagon injection?

Ease of use

  • Traditional glucagon kits provide a powder that requires dilution with a syringe and needle to add diluent. The dose must be drawn up into the syringe and injected in the arm or outer mid-thigh, IM or SC.2,4,6,8 Half the usual dose (i.e., 0.5 mg instead of 1 mg) must be given to children <25 kg (or if weight unknown and <6 years of age [Canada, <6 to
    8 years]).8,11
  • Gvoke HypoPen is a prefilled autoinjector for SC administration.17 It is administered by pushing the autoinjector down on the skin of the lower abdomen, outer thigh, or outer upper arm for five seconds.17 A window on the injector turns red when the dose has been administered.17 Gvoke PFS is a traditional prefilled syringe for SC administration.17 It is administered by removing the cap, pinching the skin at the injection site, inserting the needle into the skin at a 90angle, and pushing the plunger.17
    • Both the autoinjector and the prefilled syringe are available in two strengths: 1 mg and 0.5 mg.17 The dose is 1 mg for patients ≥12 years of age and for patients 2 to <12 years of age who weigh ≥45 kg.17 The dose for patients <45 kg who are 2 to <12 years of age is 0.5 mg.17
  • Baqsimi is a single-use, ready-to-use intranasal powder.9,19 The dose is the same for all patients ≥4 years of age.9,19
    • It is administered by inserting the device tip into one nostril, then depressing the plunger until the green line on the plunger is no longer visible.9,19
    • Inhaling is not required.9,19 Nasal congestion or decongestant use does not affect absorption.9,19
    • A demo product is available for U.S. prescribers. Contact Eli Lilly at 800-545-5979.
  • Zegalogue comes as a single-dose prefilled syringe and a single-dose prefilled autoinjector for SC administration.22
    • The dose (0.6 mg) is the same for all patients ≥6 years of age.22
    • Either product is administered SC in the lower abdomen, buttocks, front or back of the thigh, or outer upper arm.22
      • Prefilled syringe is administered by removing the cap, pinching the skin at the injection site, inserting the needle into the skin at a 45° angle, and pushing the plunger.22
      • Autoinjector is administered by pushing the autoinjector down on the skin until the yellow needle guard is fully pressed down (there may be a click) and holding for ten seconds.22 A window on the injector turns red when the dose has been administered.22


  • U.S. cost is about the same for GlucaGen HypoKit, Gvoke HypoPen, Gvoke PFS, or Baqsimi (~$280c) and slightly higher for Zegalogue (~$310c).  Gvoke, Baqsimi, and Zegalogue are available in a two-pack. (Canadian Baqsimi cost is not available at time of publication.)


  • In adults, traditional IM glucagon seems to raise blood glucose above 70 mg/dL (4 mmol/L) by about four minutes faster than Baqsimi,but this can be offset by the time it takes to prepare injectable glucagon.10 Plus, administration errors are likely with the traditional IM injection (e.g., incomplete reconstitution or injection, injection of diluent alone, bent needle, etc).10,18 In children <12 years of age, Baqsimi is about as fast as IM glucagon.9,19
  • In adults, traditional IM glucagon seems to raise blood glucose above 70 mg/dL (4 mmol/L) by about four minutes faster than Gvoke.17 But errors are more likely with traditional IM glucagon, and Gvoke is faster to use.18
  • In adults, the time to glucose recovery seems similar with traditional IM glucagon (~12 minutes) and Zegalogue (~10 minutes).22


  • Baqsimi can cause nausea (~30%) and vomiting (~15%), like injectable glucagon.8,9,19 Other common side effects include red, watery, and/or itchy eyes; stuffy, itchy, and/or runny nose; sneezing; and itchy throat.9,19
  • In adults, adverse effects associated with Gvoke include nausea (30%), vomiting (16%), and injection site reactions (7%).17
  • Zegalogue can cause nausea (~60%), vomiting (25% to 50%), headache (~10%), diarrhea (~5%), and injection-site reactions (≤5%).22

American Diabetes Association1

Diabetes Canada2

Level 1: glucose <70 mg/dL (4 mmol/L) but ≥54 mg/dL (3 mmol/L). Considered clinically important, even if asymptomatic.

Mild: autonomic (neurogenic) symptoms present. Patient can self-treat.

Level 2: glucose <54 mg/dL (3 mmol/L]

Moderate: autonomic (neurogenic) and neuroglycopenic symptoms present, but patient can self-treat.

Level 3: severe episode with impaired mental or physical function requiring assistance. Risk of seizures, unconsciousness, and death.

Severe: patient requires assistance. Loss of consciousness may occur. Glucose usually <2.8 mmol/L (50 mg/dL).

  1. Glucose sources (15 g):2,4,5,12,13,14
    • glucose tablets (3 to 4 tablets)
    • 1 heaping tablespoon (3 packets) of table sugar
    • 5 sugar cubes
    • Raisins (2 tablespoons)
    • 1/2 cup of fruit juice or regular (non-diet) soft drink
    • 6 Life Savers
    • 1 tablespoon (15 mL) of honey, syrup, or corn syrup
  1. Cost is wholesale acquisition cost (WAC). Medication pricing by Elsevier, accessed May 2021.

Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.



Study Quality


Good-quality patient-oriented evidence.*

  1. High-quality RCT
  2. SR/Meta-analysis of RCTs with consistent findings
  3. All-or-none study


Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study


Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56.]

Project Leader in preparation of this clinical resource (351108): Melanie Cupp, Pharm.D., BCPS; last modified May 2021.


  1. Standards of medical care in diabetes – 2019. Diabetes Care 2019;42(Suppl 1):S1-193.
  2. Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 practice guidelines for the prevention and management of diabetes in Canada. Can J Diabetes 2018;42(Suppl 1):S1-S325.
  3. Wei N, Zheng H, Nathan DM. Empirically establishing blood glucose targets to achieve HbA1c goals. Diabetes Care 2014;37:1048-51.
  4. American Diabetes Association. Hypoglycemia (low blood sugar). (Accessed September 1, 2019).
  5. Diabetes Canada. Hypoglycemia low blood sugar in adults. (Accessed September 1, 2019).
  6. Anon. How to administer glucagon. Diabetes Forecast. September 2017. (Accessed September 1, 2019).
  7. White JR. The contribution of medications to hypoglycemia unawareness. Diabetes Spectr 2007;20:77-80.
  8. Product information for GlucaGen Hypokit. NovoNordisk. Plainsboro, NJ 08536. July 2018.
  9. Product information for Baqsimi. Eli Lilly and Company. Indianapolis, IN 46285. July 2019.
  10. Yale JF, Dulude H, Egeth M, et al. Faster use and fewer failures with needle-free nasal glucagon versus injectable glucagon in severe hypoglycemia rescue: a simulation study. Diabetes Technol Ther 2017;19:423-32.
  11. Product monograph for GlucaGen HypoKit. Mississauga, ON L4W 5L6. June 2016.
  12. NIDDK. Low blood glucose (hypoglycemia). (Accessed September 2, 2019).
  13. Anon. Hypoglycemia? Low blood glucose? Low blood sugar? Clin Diabetes 2012;30:38.
  14. McCall AL. Insulin therapy and hypoglycemia. Endocrinol Metab Clin North Am 2012;41:57-87.
  15. Murad MH, Coto-Yglesias F, Wang AT, et al. Clinical review: drug-induced hypoglycemia: a systematic review. J Clin Endocrinol Metab 2009;94:741-5.
  16. Clinical Resource, Tramadol and Hypoglycemia. Pharmacist’s Letter/Prescriber’s Letter.February 2015.
  17. Product information for Gvoke. Xeris Pharmaceuticals. Chicago, IL 60601. September 2019.
  18. Valentine V, Newswanger B, Prestrelski S, et al. Human factors usability and validation studies of a glucagon autoinjector in a simulated severe hypoglycemia rescue situation. Diabetes Technol Ther 2019;21:522-30.
  19. Product monograph for Baqsimi. Eli Lilly Canada. Toronto, ON M5X 1B1. September 2019.
  20. Xeris Pharmaceuticals. Gvoke now approved! September 13, 2019. (Accessed October 3, 2019).
  21. Eli Lilly. Medical answers. Baqsimi (glucagon) nasal powder). August 20, 2019. (Accessed October 3, 2019).
  22. Product information for Zegalogue. Zealand Pharma A/S. Søborg, Denmark. March 2021.

Cite this document as follows: Clinical Resource, Preventing and Managing Hypoglycemia in Patients with Diabetes. Pharmacist’s Letter/Prescriber’s Letter. November 2019.

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