Type 2 diabetes: insulin therapy

Last Updated: June 23, 2023

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This tool is designed to support family physicians and primary care nurse practitioners to prescribe and manage insulin therapy for adult patients living with type 2 diabetes.

For many patients with type 2 diabetes, insulin is needed eventually. As the condition progresses, non-insulin pharmacotherapy may no longer be sufficient to maintain glycemic control over time.1,2

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Overview of insulin therapy for type 2 diabetes New

Glycemic approach1,2,8-10

* Functionally dependent patients have a Clinical Frailty Scale11 score of 4-5 on a 9-point scale. Patients with frailty have a Clinical Frailty Scale11 score of 6-8 on a 9-point scale.
** Some experts suggest using early, short-term (2-4 weeks) intensive insulin therapy in newly diagnosed type 2 diabetes patients with symptomatic hyperglycemia or those with high cardiovascular risk in acute care settings (e.g., acute MI, stroke, coronary artery bypass graft). This approach is associated with improvements in insulin resistance, beta cell function, quality of life and may induce remission when started within the first 2 years of diagnosis. It reflects expert opinion and is not included in current clinical practice guidelines.12,13
† And titrate dose of GLP1-RA as tolerated
†† Or fixed-ratio combination
††† If eGFR >30ml/min/1.73m2, may be used for cardiorenal benefit
Notes: DPP4i = dipeptidyl peptidase-4 inhibitor, eGFR = estimated glomerular filtration rate, GLP1-RA = glucagon-like peptide-1 receptor agonist, SGLT2i = sodium-glucose cotransporter-2 inhibitor
Bold = agents with stronger evidence

Different types of insulin

Basal insulin
What it is
  • Intermediate- or long-acting insulin, usually injected once daily (usually at bedtime) and used to keep blood glucose levels stable during periods of fasting (e.g., between meals, while sleeping
When to use it
  • First-line treatment for insulin-naive patients2
  • It is a simpler treatment regimen that causes less hypoglycemia and weight gain compared to premixed insulin or prandial-only regimens2
Jump to: Basal insulin options
Prandial (bolus) insulin
What it is
  • Short- or rapid-acting insulin injected at mealtime to control post-prandial (post-meal) glucose levels or for short-term correction of meal-related hyperglycemia
When to use it
  • May be added at mealtimes if glycemic control is suboptimal after 3-6 months on basal insulin (with other agents)14
  • Basal and prandial (bolus) insulin may be started together if the patient’s blood glucose level is high (≥16.7 mmol/L) and metabolic decompensation is present at initial diagnosis1
Jump to: Prandial (bolus) insulin options
Premixed insulin
What it is
  • Premixed solutions that contain two types of insulin (e.g., prandial and basal insulin)
When to use it
  • Consider for patients who cannot accommodate > 2 injections/day (e.g., those who require home care/caregiver support to administer insulin), or patients who would have difficulty adjusting insulin doses (e.g., due to cognitive ability or visual acuity)15,16
  • This dosing option is less flexible (requires a routine mealtime to prevent hypoglycemia) and offers less ability to correct for abnormal results15
Jump to: Premixed insulin options

Selecting an insulin

  • There is not a simple reason to choose one insulin over another, within each type of insulin (basal, prandial and combination)
  • When comparing insulin options, prioritize a patient’s preference in the shared decision-making process

Common properties of insulin

A1C reduction
  • Effect on A1C is 0.9-1.2% or more2
  • A1C reduction depends on dose and number of injections per day14
  • Dose increases may be limited by hypoglycemia and cost2
Impact on weight
  • All insulin associated with weight gain:
    • Effects on weight are dose-related
    • Basal insulin is associated with a weight gain of 1-2 kg* (over 6-12 months)2,17-19
      • Detemir and glargine 300 units/mL may lead to slightly less weight gain (≤1kg) than other options20,21
    • Prandial (bolus) insulin is associated with a weight gain (exact amount unknown)2
    • Premixed insulins are associated with a weight gain of 3.5-5 kg (over 6-12 months)Unclear if it is causation or correlation2,17-19
Cardiorenal outcomes
  • Insulin has a neutral effect on cardiorenal outcomes (safety but no risk reduction)1,2,22-24
Harms
  • Hypoglycemia
  • Lipohypertrophy
  • Local injection site reactions (exception: fewer with glargine vs. detemir)25
  • Allergic reactions (rare)1

Insulin specific properties

Onset, peak and duration of action
Cost and coverage
  • Cost is an important factor for many patients
  • Balance the consideration of cost against other factors when selecting insulin in the shared decision-making process
  • Patients’ coverage (e.g., Ontario Drug Benefit [ODB], Non-Insured Health Benefits [NIHB]) plays into cost
  • Originator biologic insulin lispro (Humalog 100 units/mL dosage forms), insulin aspart (NovoRapid), and insulin glargine (Lantus) will not be covered through the ODB as of December 29, 2023 without a medically necessary exemption26
Hypoglycemia risk (for basal insulin)27-29
  • Some patients benefit from choosing long-acting insulin over intermediate-acting insulin (e.g., those who do shift work, have inconsistent oral intake or those who would benefit from dosing less often)
  • For most patients, however, choosing basal insulin is not the primary factor in reducing hypoglycemia risk in a clinically meaningful way (i.e., absolute risk differences are small and the evidence is limited, making it difficult to compare basal insulins with confidence)
  • Determining other ways to reduce hypoglycemia risk is essential (see Managing hypoglycemia)

Other properties20,21,30,31

  • MortalityNot well studied (exception for prandial: studies have not shown a significant difference in mortality between rapid- and short-acting insulin)32
  • Quality of lifeNot well studied
  • Environmental impact of insulin
Consider the environmental impact of insulin
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Consider the environmental impact of insulin

The environmental impact of insulin is important to some patients.

Suggestions to reduce the environmental impact of insulin include:
  • Consider reusable insulin pens instead of single-use, prefilled insulin pens if available (see Insulin specific properties tables for insulin products that have reusable pens that take cartridges)45,47,48
  • Disposing of pens, syringes, needles and cartridges in a clearly-labeled, closable, puncture-resistant sharps container (can be obtained from a pharmacy) to prevent the disposal of ‘sharps’ into landfills48-50
  • If patients are using insulin exceeding amount allowed in 1 injection, consider a more concentrated insulin formulation (less volume required) and counsel the patient on appropriate dosing to avoid overdose45,46,49,51
  • Recycle the paper boxes, pamphlets and inserts packaged with insulin52
Biosimilar insulins
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Biosimilar insulins33-42

As of March 31, 2023, patients who are eligible for ODB program benefits and using insulin lispro (Humalog), insulin aspart (NovoRapid), and insulin glargine (Lantus) are required to transition to a biosimilar. This is a 1:1 – same dose switch.

A biosimilar is a biologic drug that is highly similar to a biologic drug that was already authorized for sale. At a reduced cost, biosimilars have equivalent clinical efficacy and safety as their originator biologic drug.

Originator biologic insulins listed above will not be covered through the ODB as of December 29, 2023, unless patients have been approved for a medically necessary exemption. To avoid gaps in coverage, during the 9-month transition period that ends in December 2023, ODB will cover both the originator and biosimilar options for patients currently receiving insulin therapy. The transition period will provide time for health care providers to become informed and subsequently have discussions with patients about biosimilar transition. This transition period will also allow time for prescribers to write a new prescription and provide time for patients to obtain their new insulin and, in some-cases, new insulin pens from their pharmacy.

Below are the biosimilar insulins that are available in Ontario:

For insulin-naive patients, consider biosimilar insulins in the table above as the first treatment option given their cost-effective advantage.

For patients on an established insulin therapy and requiring a switch to a biosimilar, consider the following approach. Submit a claim for K900A when switching patients from an originator biologic insulin to a biosimilar to receive a support payment of $61.20.

selecting insulin>biosimilar insulin

*For patients awaiting medically necessary exemption via the EAP that were already established on originator insulins therapy before March 2023; **For patients established on therapy prior to March 31, 2023 who is or has become pregnant during the biosimilar transition period between March 31, 2023 to December 28, 2023; ***For patients established on therapy prior to March 31, 2023 who is or becomes palliative requiring end-of-life care during the biosimilar transition period between March 31, 2023 to December 28, 2023.

Click here for EMR queries to identify patients who are ODB program recipients and currently prescribed NovoRapid, Humalog, and Lantus.

The patient’s new biosimilar insulin pen(s) may look different from the originator insulin. Encourage patients to consult their pharmacist to minimize confusion about the change in appearance, especially if they use different pens for basal and bolus therapy. If switching both basal and bolus therapy to biosimilars, consider temporally separate switches to reduce medication errors.

Medically necessary exemptions

To ensure no gaps in patient coverage through the ODB, submit EAP requests promptly through the Special Authorization Digital Information Exchange. Requests can also be faxed using the EAP form to 1-866-811-9908 (toll-free) or 416-327-7526 (Toronto area)

Biosimilar insulins talking tips
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Biosimilar insulins talking tips 36-39

  • This new insulin has been approved and reviewed by Health Canada and is basically the same as your previous one.
  • Although your new biosimilar insulin pen may look and feel a little bit different, it still works the same as the insulin you were taking.
  • Use this new insulin the exact same way and same dose as your previous one. Continue all your other medications the same way too.
  • When you get your prescription filled for the first time, ask your pharmacist to show you how to attach the needles and inject. You can also reach out to them if you have any more ongoing questions.
  • [For patients who are not supposed to switch to a biosimilar insulin – i.e., those who have characteristics or circumstances, temporary or otherwise, that would contribute to negatively impacting health outcomes] I need to add an extra code to your prescription so you can stay on this medication.
  • Originator biologic insulin lispro (Humalog 100 units/mL dosage forms), insulin aspart (NovoRapid), and insulin glargine (Lantus) will not be covered through the ODB as of December 29, 2023 without a medically necessary exemption.
Consider the affordability of insulin
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Consider the affordability of insulin57

  • All insulin options below have ODB and NIHB coverage unless otherwise specified
  • All insulin 100 units/mL, unless otherwise specified

* Prices reflect the cost to the customer and include markup and dispensing fee (the cost per dosage form and the 100-day cost both include one dispensing fee and reflect the usual pharmacy practice of dispensing a full box; e. g., 5x3mL pens). The cost for a usual dose assumes a 100kg patient.
** See Insulin Options cards for details on the limited use restrictions.

Explore patient reimbursement opportunities for insulin related supplies
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Reimbursement opportunities

Support patients to explore reimbursement opportunities for blood glucose monitoring supplies, pen needles and syringes.

Ontario Ministry of Health’s Ontario Drug Benefit (ODB) program
  • Offers all ODB recipients on insulin reimbursement for a flash glucose monitoring system (specifically, the FreeStyle Libre and FreeStyle Libre 2 systems), including:
    • 1 reader/patient (otherwise costs $65)
    • 33 sensors/year/patient (otherwise costs $2,457.54/year)
  • Offers all ODB recipients coverage for a set number of blood glucose test strips annually, depending on their diabetes management approach:
    • 3,000 test strips/year for patients on insulin
    • 400 test strips/year for patients on non-insulin pharmacotherapy with higher risk of causing hypoglycemia (e.g., glyburide, gliclazide)
    • 200 test strips/year for patients on non-insulin pharmacotherapy with lower risk of causing hypoglycemia (e.g., acarbose, metformin, canagliflozin, empagliflozin, linagliptin, saxagliptin, sitagliptin)
    • 200 test strips/year for patients on diet/lifestyle therapy only
Diabetes Canada’s Ontario Monitoring for Health Program14

Offers patients of all ages 75% reimbursement for:

  • Blood glucose test strips and lancets – up to a maximum of $920/year
  • Blood glucose meter – up to a maximum of $75/every 5 years
  • Talking blood glucose meter – up to a maximum of $300/every 5 years (note: a letter from a doctor is required to confirm visual impairment)
Ontario Ministry of Health’s Assistive Devices Program43
  • Offers patients 65+ an annual grant ($170/year) to cover the costs of needles and syringes used to inject insulin
  • Consider less expensive insulin dosage forms (e.g., vials) for patients 65+ who obtain syringe coverage

 

Non-Insured Health Benefits Program44
  • Starting April 25, 2023, the NIHB Program will include coverage for Dexcom G6, FreeStyle Libre, and FreeStyle Libre 2 CGM systems as limited use benefits for patients managing insulin-dependent diabetes
  • Prior approval and coverage criteria listed in the Drug Benefit List apply
  • NIHB also covers diabetes test strips, allowing up to 800 strips per 100 days for insulin-managing patients
  • Coverage allows for one reader every three years and 14 sensors every six months

Insulin options

Basal insulin1,15,46,53-59,103
Scroll (left-right) for details
  • Intermediate acting
    NPH (Humulin® N)

    100 units/mL

    Activity profile

    • Onset:1-2h
    • Peak: 5-8h
    • Duration: 14-18h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • 3mL prefilled pens: $204
    • 3mL cartridges: $204
    • 10mL vial: $158

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • 3mL prefilled pens: $107
    • 3mL cartridges: $107
    • 10mL vial: $84
    Comments
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    Comments

    • More erratic absorption vs. long-acting analogues
    • If a patient is dosed bid, the need for a lunch dose of prandial (bolus) insulin may be delayed
    • Max units/dose: 60 for prefilled and reusable pensThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Intermediate acting
    NPH (Novolin® ge)

    100 units/mL

    Activity profile

    • Onset: 1-2h
    • Peak: 5-8h
    • Duration: 14-18h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • 3mL cartridges: $188
    • 10mL vial: $145

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • 3mL prefilled pens: $98
    • 10mL vial: $77
    Comments
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    Comments

    • More erratic absorption vs. long-acting analogues
    • If a patient is dosed bid, the need for a lunch dose of prandial (bolus) insulin may be delayed
    • Max units/dose: 60 for prefilled and reusable pensThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Intermediate acting
    NPH pork (Hypurin®)

    100 units/mL

    Not on Ontario drug formulary

    Activity profile

    • Onset: 1-3h
    • Peak: 6-12h
    • Duration: 24-48h

    Coverage

    • ODB X
    • NIHB X

    Dosage forms

    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • $718

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • $355
    Comments
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    Comments

    • Not often used in practice due to lack of coverage, cost and inconvenience  with vial/syringes
  • Long-acting
    Degludec (Tresiba®)

    100 units/mL

    Activity profile

    • Onset: 1h
    • Peak: No peak
    • Duration: 42h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • $418

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • $213
    Comments
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    Comments

    • Duration useful for shift workers
    • Can increase the dose by increments of 1 unit
    • Max units/dose: 80 for prefilled penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Long-acting
    Degludec (Tresiba®)

    200 units/mL

    Activity profile

    • Onset: 1h
    • Peak: No peak
    • Duration: 42h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 3x3mL prefilled pens

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • $418

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • $213
    Comments
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    Comments

    • Duration useful for shift workers
    • 200 units/mL can be started if larger doses are required
    • Can increase the dose by increments of 2 units
    • Bioequivalent to degludec 100 units/mL
    • Max units/dose: 160 for prefilled penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Long-acting
    Detemir (Levemir®)

    100 units/mL

    Activity profile

    • Onset: 1.5h
    • Peak: Flat, no discernable peak
    • Duration: 6-24h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • $414

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • $213
    Comments
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    Comments

    • Duration of action may be shorter at lower doses and may require bid dosing (cut-off varies by patient)
    • If a patient is experiencing nocturnal hypoglycemia with a bedtime dose, lower the dose, inject the dose in the morning or split daily dose to bid
    • Max units/dose: 80 for prefilled pen,  60 for reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Long-acting
    Glargine (BasaglarTM)

    100 units/mL

    Activity profile

    • Onset: 1.5h
    • Peak: Flat, no discernable peak
    • Duration: 24h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • 3mL prefilled pens: $288
    • 3mL cartridges: $288

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • 3mL prefilled pens: $148
    • 3mL cartridges: $148
    Comments
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    Comments

    • Acidic formulation may cause irritation
    • BasaglarTM and Semglee® are biosimilars to Lantus®  
    • If a patient is experiencing nocturnal hypoglycemia with a bedtime dose, lower the dose or inject the dose in the morning
    • Max units/dose: 80 for prefilled pens, 60 for BasaglarTM reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Long-acting
    Glargine (Lantus®)

    100 units/mL

    Activity profile

    • Onset: 1.5h
    • Peak: Flat, no discernable peak
    • Duration: 24h

    Coverage

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • 3mL prefilled pens: $349
    • 3mL cartridges: $349
    • 10mL vial: $348

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • 3mL prefilled pens: $179
    • 3mL cartridges: $179
    • 10mL vial: $178
    Comments
    Close

    Comments

    • Acidic formulation may cause irritation
    • BasaglarTM and Semglee® are biosimilars to Lantus®
    • If a patient is experiencing nocturnal hypoglycemia with a bedtime dose, lower the dose or inject the dose in the morning
    • Max units/dose: 80 for prefilled pens, 80 for Lantus® reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Long-acting
    Glargine (Semglee®)

    100 units/mL

    Activity profile

    • Onset: 1.5h
    • Peak: Flat, no discernable peak
    • Duration: 24h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • $243

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • $126
    Comments
    Close

    Comments

    • Acidic formulation may cause irritation
    • BasaglarTM and Semglee® are biosimilars to Lantus®
    • If a patient is experiencing nocturnal hypoglycemia with a bedtime dose, lower the dose or inject the dose in the morning
  • Long-acting
    Glargine (Toujeo®)

    300 units/mL

    Activity profile

    • Onset: 1.5h
    • Peak: Flat, no discernable peak
    • Duration: Up to 36h

    Coverage

    • ODB ✓
    • NIHB ✓ (1.5mL and 3mL)

    Dosage forms

    • 3×1.5mL or 5×1.5mL prefilled pens
    • 3x3mL prefilled pens

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*

    • 1.5mL prefilled pens: $332
    • 3mL prefilled pens: $332

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*

    • 1.5mL prefilled pens: $170
    • 3mL prefilled pens: $170
    Comments
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    Comments

    • Recommend for patients who require >20 units of basal insulin/day, and counsel on change of concentration
    • NOT bioequivalent to glargine 100 units/mL (longer duration and delayed peak; starting dose when switching can be the same but a higher daily dose may eventually be needed)
    • If a patient is experiencing nocturnal hypoglycemia with a bedtime dose, lower the dose or inject the dose in the morning
    • Max units/dose: 80 for 1.5mL prefilled pen, 160 for 3mL prefilled penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Ultra-long-acting
    Icodec (Awiqli®)

    700 units/mL

    Activity profile

    • 2-4 weeks to steady state. At this point it acts as a circulating insulin reservoir.
    • Glucose-lowering effect covers the full weekly dosing interval.
    • Peak: 2-4 days
    • Half-life: ~ 1 week

    Coverage

    • ODB X
    • NIHB X

    Dosage forms

    • 1x1mL prefilled pen (sample pack only)
    • 1×1.5mL prefilled pen
    • 1x3mL prefilled pen

    Cost for usual dose (350 units/week for 100 days supply; basal alone)*

    • 1.5mL prefilled pens: $466
    • 3mL prefilled pens: $566

    Cost for usual dose (175 units/week for 100 days supply; basal + bolus; cost is for basal component)*

    • 1.5mL prefilled pens: $285
    • 3mL prefilled pens: $310
    Comments
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    Comments

    • Once weekly administration; useful for patients with barriers to daily insulin dosing
    • Can increase the dose by increments of 10 units
    • Max units/dose: 700
    • Discard 12 weeks after first use or after storing at room temperature

Prandial (bolus) insulin1,15,45,53,57,60,61,62

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  • Rapid-acting
    Aspart (NovoRapid®)

    100 units/mL

    Activity profile

    • Onset: 9-20 min
    • Peak: 1-3h
    • Duration: 3-5h

    Coverage

    Dosage forms

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL cartridges: $121
    • 10mL vial: $92
    Comments
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    Comments

    • Inject immediately (not more than 5-10 minutes) before or immediately after a meal
    • Max units/dose: 80 for prefilled pen, 60 for reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting
    Aspart (Kirsty®)

    100 units/mL

    Activity profile

    • Onset: 10-20 min
    • Peak: 1-3h
    • Duration: 3-5h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens

    Cost for usual dose (25 units/day for 100 days supply)*

    • $87
    Comments
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    Comments

    • Inject immediately (not more than 5-10 minutes) before or immediately after a meal
    • Kirsty® is biosimilar to NovoRapid®
    • Max units/dose: ** 80 for prefilled pen
  • Rapid-acting
    Aspart (TrurapiTM)

    100 units/mL

    Activity profile

    • Onset: 10-20 min
    • Peak: 1-3h
    • Duration: 3-5h

    Coverage

    • ODB ✓ (prefilled pens and cartridges)
    • ODB X (vial)
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL prefilled pens: $91
    • 3mL cartridges: $91
    • 10mL vial: $96
    Comments
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    Comments

    • Inject immediately (not more than 5-10 minutes) before or immediately after a meal
    • Trurapi® is biosimilar to NovoRapid®
    • Max units/dose: 80 for prefilled pen, 60 for reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting
    Aspart (Fiasp®)

    100 units/mL

    Not on Ontario drug formulary

    Activity profile

    • Onset: 4 min
    • Peak: 0.5-1.5h
    • Duration: 3-5h

    Coverage

    • ODB X
    • NIHB X

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL prefilled pens: $136
    • 3mL cartridges: $129
    • 10mL vial: $99
    Comments
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    Comments

    • Faster acting insulin
    • Suggested initial dose for type 2 diabetes in adults is 4 units at one or more meals
    • Inject at the start of the a meal (up to 2 minutes before meal) or within 20 minutes after starting the meal
    • Max units/dose: 80 for  prefilled pen, 60 for reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting
    Glulisine (Apidra®)

    100 units/mL

    Activity profile

    • Onset: 10-15 min
    • Peak: 1-1.5h
    • Duration: 3.5-5h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL prefilled pens: $106
    • 3mL cartridges: $105
    • 10mL vial: $82
    Comments
    Close

    Comments

    • Inject within 15 minutes before or within 20 minutes after starting a meal
    • Max units/dose: 80 for prefilled and reusable pensThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting
    Lispro (Humalog®)

    100 units/mL

    Activity profile

    • Onset: 10-15 min
    • Peak: 0.75-2.5h
    • Duration: 3.5-4.75h

    Coverage

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL prefilled pens: $129
    • 3mL cartridges: $128
    • 10mL vial: $100
    Comments
    Close

    Comments

    • Inject within 15 minutes before a meal or within 20 minutes after starting the meal
    • Admelog® is biosimilar to Humalog®
    • Max units/dose: 60 for Humalog® prefilled and reusable pensThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting
    Lispro (Admelog®)

    100 units/mL

    Activity profile

    • Onset: 10-15 min
    • Peak: 0.75-2.5h
    • Duration: 3.5-4.75h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL prefilled pens: $91
    • 3mL cartridges: $91
    • 10mL vial: $71
    Comments
    Close

    Comments

    • Inject within 15 minutes before a meal or within 20 minutes after starting the meal
    • Admelog® is biosimi-lar to Humalog®
    • Max units/dose: 80 for Admelog® prefilled and reusable pensThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting
    Lispro (Humalog®)

    200 units/mL

    Activity profile

    • Onset: 10-15 min
    • Peak: 0.75-2.5h
    • Duration: 3.5-4.75h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens

    Cost for usual dose (25 units/day for 100 days supply)*

    • $120
    Comments
    Close

    Comments

    • Higher concentration requires smaller volume
    • Recommend for patients who require >20 units of prandial (bolus) insulin/day, and counsel on change of concentration
    • Max units/dose: 60 for prefilled penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Short-acting
    Regular insulin (Humulin® R)

    100 units/mL

    Activity profile

    • Onset: 30-60 min
    • Peak: 2-4h
    • Duration: 5-8h

    Coverage

    • ODB ✓ (prefilled pen and cartirdge)
    • ODB X (vial)
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pen
    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL prefilled pen: $107
    • 3mL cartridges: $107
    • 10mL vial: $84
    Comments
    Close

    Comments

    • Inject 15-30 minutes before meals
    • Max units/dose: 60 for Humulin R® resuable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Short-acting
    Regular insulin (Novolin®ge Toronto)

    100 units/mL

    Activity profile

    • Onset: 30-60 min
    • Peak: 2-4h
    • Duration: 5-8h

    Coverage

    • ODB ✓ (prefilled pen and cartirdge)
    • ODB X (vial)
    • NIHB ✓

    Dosage forms

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*

    • 3mL cartridges: $96
    • 10mL vial: $76
    Comments
    Close

    Comments

    • Inject 15-30 minutes before meal
    • Max units/dose: 60 for Novolin®ge Toronto resuable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Short-acting
    Regular insulin (Entuzity®)

    500 units/mL

    Not on Ontario drug formulary

    Activity profile

    • Onset: 3-58 min
    • Peak: 0.5-8h
    • Duration: 17-24h

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 2x3mL prefilled pens

    Cost for usual dose (25 units/day for 100 days supply)*

    • $95
    Comments
    Close

    Comments

    • Inject 15-30 minutes before meals
    • Entuzity® should be reserved for patients who require > 200 units/day and delivers  insulin in 5-unit increments
    • Entuzity® has a unique pharmacokinetic profile with an onset similar to regular insulin and a duration similar to some basal/premixed insulins
    • Max units/dose: 300 for Entuzity® prefilled penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.

Premixed insulin and GLP1-RA + insulin combinations15,45,53,54,57

The choice of premixed insulin will depend on the patient’s dosing requirements for basal and prandial (bolus) insulin and which type of prandial insulin is preferred by the patient and provider. Refer to individual components above for onset, peak and duration.

Scroll (left-right) for details
  • Short-acting + intermediate-acting
    Premixed regular/NPH (Humulin® 30/70)

    100 units/mL

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply)*

    • 3mL cartridges: $197
    • 10mL vial: $150
    Comments
    Close

    Comments

    • Contain both short-acting regular prandial (bolus) insulin and intermediate-acting NPH basal insulin
    • The numbers in the product name (30/70) refer to the percentage of each type of insulin contained in the product (e.g., Novolin ge 30/70® contains 30% regular insulin and 70% NPH insulin)
    • Inject bid 30 minutes before eating
    • Max units/dose: 60 for reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Short-acting + intermediate-acting
    Premixed regular/NPH (Novolin®ge 30/70)

    100 units/mL

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply)*

    • 5x3mL cartridges: $173
    • 10mL vial: $140
    Comments
    Close

    Comments

    • Contain both short-acting regular prandial (bolus) insulin and intermediate-acting NPH basal insulin
    • The numbers in the product name (30/70) refer to the percentage of each type of insulin contained in the product (e.g., Novolin ge 30/70® contains 30% regular insulin and 70% NPH insulin)
    • Inject bid 30 minutes before eating
    • Max units/dose: 60 for reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting + intermediate-acting
    Aspart/aspart protamine suspension (Novomix® 30)

    100 units/mL

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*

    • $203
    Comments
    Close

    Comments

    • Contains 30% rapid-acting prandial (bolus) insulin aspart and 70% intermediate-acting insulin aspart protamine crystals
    • Inject within 10 minutes before eating
    • Max units/dose: 60This reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting + intermediate-acting
    Lispro/lispro protamine suspension (Humalog® Mix25)

    100 units/mL

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*

    • 3mL prefilled pens: $205
    • 3mL cartridges: $206
    Comments
    Close

    Comments

    • Contains a mix of rapid-acting prandial (bolus) insulin lispro (either 25% to 50%) and intermediate acting insulin lispro protamine suspension (either 75% or 50%)
    • Inject within 10 minutes before eating
    • Max units/dose: 60 for prefilled and reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • Rapid-acting + intermediate-acting
    Lispro/lispro protamine suspension (Humalog® Mix50)

    100 units/mL

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL prefilled pens
    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*

    • 3mL prefilled pens: $201
    • 3mL cartridges: $203
    Comments
    Close

    Comments

    • Contains a mix of rapid-acting prandial (bolus) insulin lispro (either 25% to 50%) and intermediate acting insulin lispro protamine suspension (either 75% or 50%)
    • Inject within 10 minutes before eating
    • Max units/dose: 60 for prefilled and reusable penThis reflects the maximum amount given for 1 injection, not the maximum amount of insulin that is required. Multiple injections may be required to achieve blood glucose targets.
  • GLP1-RA + insulin combinations (not premixed insulins)
    Degludec/liraglutide (Xultophy®)

    100 units/mL

    Not on Ontario drug formulary

    Coverage

    • ODB X
    • NIHB X

    Dosage forms

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*

    • $1,065
    Comments
    Close

    Comments

    • Contains a mix of long-acting basal insulin degludec and GLP1-RA liraglutide
    • Inject 16 units/0.58mg – 50 units/1.8mg SC daily
    • Administer at any time of the day (but same time every day) independent of meals
    • Max: 50 units insulin daily
  • GLP1-RA + insulin combinations (not premixed insulins)
    Glargine/lixisenatide (Soliqua®)

    100 units/mL

    Coverage

    • ODB ✓
    • NIHB ✓

    Dosage forms

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*

    • $624
    Comments
    Close

    Comments

    • Contains a mix of long-acting basal insulin glargine 100 units/mL and GLP1-RA lixisenatide
    • Inject 15 units/5μg – 60 units/20μg SC daily
    • Administer within 1 hour before the first meal of the day
    • Max: 60 units insulin daily

* Prices reflect the cost to the consumer and include a markup and dispensing fee (the cost per dosage form and the 100-day cost both include one dispensing fee and reflect the usual pharmacy practice of dispensing a full box or vial; e.g., 5x3mL pens). The cost for a usual dose assumes a 100 kg patient. The price for vials does not include the cost of syringes.
✓ = general benefit, ? = not a benefit, bid = twice daily, h = hour, kg = kilogram, max = maximum, μg = microgram, mg = milligram, mL = milliliter, NIHB = non-insured health benefits for First Nations and Inuit, NPH = neutral protamine Hagedorn, ODB = Ontario Drug Benefit, SC = subcutaneous

Initiating and titrating insulin

Practical tips for discussing insulin initiation with patients57

  • Start the insulin discussion early (e.g., at diagnosis and regular follow-up appointments)
  • Ensure patients understand that insulin is not a punishment or indication of treatment failure, and that many patients end up on insulin later in life
  • Consider patient values regarding the benefits/harms of adding insulin relative to the intensity of glycemic control (e.g., some patients may opt for moderate control without insulin)
  • Provide information on the benefits of insulin therapy (e.g., lower blood glucose, no gastrointestinal upset, reduces nocturnal urination secondary to hyperglycemia)
  • Understand the patient’s barriers or concerns about starting insulin
  • Consider framing starting insulin as a “trial”, with a set duration (e.g., 1 month), with a plan to discuss and adjust as needed
  • To increase their confidence before starting injection(s), give the patient time to try different insulin pens and needles
Talking points57
  • “For most people living with diabetes, insulin is required at some point in their life as part of their management plan.”
  • “Since you are not feeling well now, adding insulin may help you feel better sooner.” (Offer the patient examples of their symptoms, e.g., blurred vision, fatigue, low energy. increased urination).”
  • “The insulin needle injection hurts less than a fingerprick when checking blood glucose.”
  • “Would you be open to trying insulin therapy for 1 month to see how it works for you?”

Insulin initiation checklist

Counsel patients on:
  • Insulin injection frequency and timing
  • Proper and safe insulin injection techniques, pen needle use and insulin storage
    • Consider connecting the patient to a qualified person/program to provide this counselling (e.g., Certified Diabetes Educator, Diabetes Education Program/Centre or collaborative support [registered nurse, nurse practitioner, pharmacist, dietitian] in the office or community). See Local services for patients living with type 2 diabetes
  • Hypoglycemia prevention and treatment (see Managing hypoglycemia)
  • Frequency of self-monitoring of blood glucose (See Self monitoring blood glucose frequency and pattern tool)63
  • Options for blood glucose self-monitoring devices/systems (e.g., blood glucose meter, flash glucose monitoring system, continuous glucose monitoring system)
  • Changes to current non-insulin pharmacotherapy dosing, if applicable (see Insulin initiation and titration process)
Storing insulin64,65

 Unopened insulin

  • Should be stored in the fridge between 2ºC and 8ºC
  • Is safe to use until the expiration date

In-use insulin

  • Should be stored at room temperature, avoiding contact  with direct sunlight
  • Is generally good for up to 28 days (detemir and glargine 300 units/mL are safe at room temperature for 42 days, degludec is safe at room temperature for 56 days, and icodec is safe at room temperature for 12 weeks) – counsel patient  to write the first date of use on the label

When to discard

  • If it has been frozen
  • If kept out of the fridge for longer than the specified period
  • If exposed to temperatures greater than 30ºC
  • If it has expired

Safe insulin injection techniques and pen needle use66 

  • Injection sites and rotation (proper injection technique can significantly improve A1C and reduce erratic insulin effects and hypoglycemia)
    • Divide injection area into zones, use 1 zone per week and move clockwise, spacing out each injection within any zone by 1-2 cm
    • Avoid intramuscular injection
      • Abdomen, thighs and buttocks as the preferred self-injection areas
      • Avoid the arms
    • Avoid injecting within 2-3 cm of the umbilicus
    • Avoid injecting in altered skin (e.g., skin with surgical scars, stretch marks, lipohypertrophy, tattoos, moles, skin conditions)
  • Pen needles
    • Insulin should be brought to room temperature before injecting
    • Inject pen needles at a 90˚ angle
    • Avoid reusing pen needles or syringes
    • Use pen needle sized 4-6 mm for all patients regardless of body mass index (4 mm pen needles provide the equivalent A1C control as both as 8 mm and 12 mm pen needles in people with obesity who are taking large doses of insulin)67
  • See FIT technique plus for a series of patient educational tools on best practice injection technique and pen needle use

Injection site rotation

Pen needle wear after use

Insulin initiation and titration

Support patients to self-monitor
  • Fasting blood glucose and 2-hour post-prandial blood glucose (See Self-monitoring blood glucose frequency and pattern tool for individualized timing63)
  • Blood glucose levels in the middle of the night (1-2 times/month) to determine if they are experiencing nocturnal hypoglycemia57
  • Blood glucose at least 2 times/day to safely titrate premixed insulin14
Targets2,14

See Insulin prescription for examples68

Fasting blood glucose
  • Usual: 4.0-7.0 mmol/L (if A1C is not at target, consider a target of 4.0-5.5 mmol/L, balanced against the risk of hypoglycemia)
  • Functionally dependent/frail:* targets may be relaxed
Pre-prandial blood glucose
  • Usual: 4.0-7.0 mmol/L
  • Functionally dependent:* 5.0-8.0 mmol/L
  • Frail/dementia:* 6.0-9.0 mmol/L
Post-prandial blood glucose
  • Usual: 5.0-10.0 mmol/L
  • Functionally dependent:* < 12.0 mmol/L
  • Frail/dementia:* < 14.0 mmol/L

Insulin initiation and titration process

basil insulin

Initiating and titrating flow chart

Initiating and titrating flow chart

prandial (bolus) traffic light

Initiating and titrating flow chart

prandial initiating and titrating flow chart

*As effective as starting prandial insulin at all meals, but with lower risk of hypoglycemia and greater patient satisfaction at 1 year57

premixed insulin and GLP1-RA-insulin traffic light

Initiating and titrating flow chart

Premixed insulin initiating and titrating flow chart

Switching insulin New

When to switch insulin57

Consider switching to insulin if patient presents the following:

  • Hypoglycemia
  • Weight gain
  • Hyperglycemia
  • Higher or more concentrated dose required
  • Cost and coverage concerns, if raised by the patient
  • Patient convenience

How to switch insulin15,28

  • Confirm current insulin dose, including agent, concentration and dosage form used
  • Switching insulin often involves switching insulin pen devices
  • Counsel patients to temporarily increase the frequency of blood glucose monitoring during switch
  • Two approaches to switch insulin (20% dose reduction or ‘unit-to-unit’), with a third approach to switch from daily to weekly insulin
Switch insulin using a 20% dose reduction15,28
Switch insulin ‘unit-to-unit’11,22,102,103
Switch from daily to weekly insulin (basal only)103,104
Initial dosing when switching from daily basal insulin*

Week 1**

7x daily basal dose.

If patient has a history of poor glycemic control/hypoglycemia, 10.5x daily basal dose (first dose only).

Week 2

7x daily basal dose + titration as needed (see Insulin initiation and titration process).

If week 1 dose was 10.5x daily basal dose, decrease to 7x daily basal dose for week 2.

Week 3 onward

Ongoing titration as needed (see Insulin initiation and titration process).

*Rounded to the nearest 10 units.
**First weekly dose should be taken the day following the last dose of daily basal insulin.

Managing hypoglycemia

It is safer and more effective to prevent hypoglycemia than to t reat it after hypoglycemia occurs.11 Counsel patients who are at high-risk for hypoglycemia on how to prevent low blood glucose.14

Hypoglycemia is defined by:14
  1. The development of neurogenic or neuroglycopenic symptoms (see Hypoglycemia symptoms)
  2. A low blood glucose level (<4.0 mmol/L for people with diabetes treated with insulin or an insulin secretagogue)
  3. The presence of symptoms that resolve following the intake of carbohydrates

Hypoglycemia symptoms14

Neurogenic (autonomic)
  • Trembling
  • Palpitations
  • Sweating*
  • Anxiety
  • Hunger
  • Nausea
  • Tingling
Neuroglycopenic
  • Difficulty concentrating
  • Confusion
  • Weakness
  • Drowsiness
  • Vision changes
  • Difficulty speaking
  • Headache*
  • Dizziness
  • Disturbed sleep*
  • Abnormal dreams*

*Symptoms of nocturnal hypoglycemia

Reducing hypoglycemia risk

Education
Monitor
  • Support patients to self-monitor blood glucose more often
  • Consider a flash or continuous glucose monitoring system14
    • If readings are < 4.0mmol/L, test the glucose monitoring system accuracy using a fingerprick
  • For nocturnal hypoglycemia: advise patients to monitor their blood glucose levels periodically at the peak action time of their overnight insulin (use a glucose monitor that gives al erts based on blood glucose levels, e.g., DexCom® 6, FreeStyle Libre® 2 or FreeStyle Libre® combined with NightRider BluCon®)14
Reassess targets
  • Reassess whether targets are appropriate for the patient
  • If patient has hypoglycemia unawareness or pseudohypoglycemia, may consider less stringent glycemic targets with avoidance of hypoglycemia signs or symptoms for up to 3 months14
Adjust medication
  • Consider using medication (see Type 2 diabetes: non-insulin pharmacotherapy) and insulin (e.g., long-acting insulin) with a lower risk of hypoglycemia14
  • Stop sulfonylureas when prandial (bolus) insulin is added to basal insulin2
  • Consider reducing basal insulin dose by 10-20% if adding another non-insulin agent (e.g., GLP1-RA, SGLT2i)74
  • Adjust insulin regimen or ratio75

Risk factors for severe hypoglycemia

Patient risk factors
  • Advancing age and frailty14,76
  • Female gender77
  • Low A1C (<6.0%)14
  • Hypoglycemia unawareness14**
  • Prior episode of severe hypoglycemia14
  • Long duration of diabetes (insulin insufficiency)76
  • Neuropathy14
  • Renal impairment (for eGFR <30, consider adjusting insulin dose and timing to minimize insulin stacking)14,76
  • Cognitive impairment14
  • Poor health literacy14
  • Food insecurity or erratic eating patterns3, 62
Medication risk factors
  • Use of insulin78
  • Long-term use of insulin therapy14
  • Basal insulin component too high78
  • Prandial (bolus) insulin doses not adjusted for physical activity, carbohydrate intake or skipped meals 76
  • Not adjusting medications after weight loss or withdrawal of medications that raise blood glucose (e.g., corticosteroids)76
  • Insulin mistakes (e.g., administering prandial (bolus) insulin at bedtime on an empty stomach instead of basal insulin)
  • Insulin stacking (e.g., injecting insulin correction within 3 hours of a previous correction)
  • Overbasalization (e.g., titration of basal insulin beyond an appropriate dose in an attempt to achieve glycemic targets)69
  • Lipohypertrophy73
  • Drugs that cause or mask symptoms of hypoglycemia (e.g., anti-hyperglycemics, beta blockers, ACE inhibitors, ethanol, fluoroquinolones, salicylates)79

**Hypoglycemia unawareness occurs when the threshold for the development of neurogenic warning symptoms is close to, or lower than, the threshold for the neuroglycopenic symptoms, such that the first sign of hypoglycemia is confusion or loss of consciousness. Frequent hypoglycemia can lead to hypoglycemia unawareness by decreasing normal responses to hypoglycemia. Hypoglycemia unawareness can be improved or reversed by strictly avoiding hypoglycemia for up to 3 months.14

Range of hypoglycemia severity14

Treating hypoglycemia14

  • Hypoglycemia treatment aims to promptly increase low blood glucose to a safe level to eliminate the risk of injury and relieve symptoms
  • Avoid over-treatment, which can result in rebound hyperglycemia and weight gain

Select for treatment details

  1. Oral ingestion of 15g carbohydrate (glucose or sucrose tablets/ solution preferred*)14
  2. Re-test blood glucose in 15 minutes. If the blood glucose level remains at <4.0 mmol/L, re-treat with another 15g carbohydrate14
  3. Once the hypoglycemia is reversed, eat the usual meal/snack tha t is due at that time of day. If a meal is >1 hour away, eat a snack with 15g carbohydrate and a protein source14

*People taking an alpha glucosidase inhibitor (acarbose) must use glucose (dextrose) tablets or, if unavailable, milk or honey to treat hypoglycemia.14

Conscious patient

  1. Oral ingestion of 20g carbohydrate (glucose tablets or equivalent preferred*)14
  2. Re-test blood glucose in 15 minutes. If the blood glucose level remains at <4.0 mmol/L, re-treat with another 15g carbohydrate14
  3. Once the hypoglycemia is reversed, eat the usual meal/snack that is due at that time of day. If a meal is >1 hour away, eat a snack with 15g carbohydrate and a protein source14

Unconscious patient (with no intravenous access)

  1. Caregiver or support person should administer 1mg of glucagon subcutaneously or intramuscularly, or 3mg intranasally (see Glucagon as treatment for severe hypoglycemia)14,80
  2. Caregiver or support person should call for emergency services and notify the care team as soon as possible14
  3. Once the hypoglycemia is reversed, patient should eat the usual meal/snack that is due at that time of day. If a meal is >1 hour away, eat a snack with 15g carbohydrate and a protein source14

Unconscious patient (with intravenous access)

  1. Caregiver or support person should administer 10-25g (20–50 mL of D50W) glucose intravenously over 1-3 minutes14
  2. Caregiver or support person should call for emergency services and notify the care team as soon as possible14
  3. Once the hypoglycemia is reversed, patient should eat the usual meal/snack that is due at that time of day. If a meal is >1 hour away, eat a snack with 15g carbohydrate and a protein source14

*People taking an alpha glucosidase inhibitor (acarbose) must use glucose (dextrose) tablets or, if unavailable, milk or honey to treat hypoglycemia.14

Examples of 15g of carbohydrate:2
  • 4 glucose/sucrose tablets (most tablets are 4g each)
  • 15mL (1 tbsp) of sugar dissolved in water
  • 3 packets of sugar from fast food/restaurants
  • 5 cubes of sugar
  • 150 mL (2/3 cup) of juice or regular soft drink
  • 6 Life Savers® (each is 2.5g of carbohydrate)
  • 15 mL (1 tbsp) of honey
Troubleshooting hypoglycemia when A1C is above target
  • Treat the low blood glucose first
  • Identify reasons for low blood glucose (e.g., skipped meal, exercise, too much insulin, sulfonylurea)
  • Review with the patient how to properly treat low blood glucose (some patients may take too much carbohydrate causing hyperglycemia)

Glucagon as treatment for severe hypoglycemia

  • Glucagon should be prescribed to patients who experience or are at high risk of experiencing severe.hypoglycemia (e.g., those on long-term use of insulin who produce little to no insulin on their own, those at risk of insulin mistakes)
  • Glucagon is to be administered by a caregiver or support person (1mg subcutaneously/intramuscularly or 3mg intranasally) to a patient experiencing a severe hypoglycemic reaction when impaired consciousness precludes oral carbohydrates14,80
  • Intranasal and intramuscular/subcutaneous glucagon are similarly effective. Some studies however, demonstrate that intramuscular/subcutaneous glucagon may be slightly more effective.82,83 Intranasal glucagon may be preferred due to ease of use, and intramuscular/subcutaneous glucagon may be preferred due to lower cost.84
Scroll (left-right) for details
  • Intranasal glucagon (Baqsimi®) 80

    Coverage53,54

    Dosage forms53

    • 3mg prefilled device

    Usual dose

    • 3mg IN80

    Cost for usual dose

    • T: $165
    Comments
    Close

    Comments

    Time to treatment response:

      • Mean: 16.2 mins83
      • Median: 10 (range 5-25) mins83
    • Time required to administer: 1 min84
    • Inhalation is not required by the patient83
    • Advantages:
      • Preferred due to ease of use84
      • Higher rate of administration success83
      • No refrigeration required80
    • Disadvantages:
      • Administration-related oronasopharyngeal and eye side effects (e.g., nasal discomfort, nasal congestion, nasal itching, sneezing, increased lacrimation, upper respiratory tract irritation)83
      • Other side effects: nausea, vomiting, headache, fatigue83,84
  • Intramuscular/ subcutaneous glucagon (GlucaGen®, GlucaGen HypoKit®)85,86

    Coverage53,54

    • ODB ✓
    • NIHB ✓

    Dosage forms53

    • 1mg vial (HypoKit® includes vial and prefilled syringe with diluent)

    Usual dose

    • 1mg IM/SC85,86

    Cost for usual dose

    • G: $122
    • T: $124
    Comments
    Close

    Comments

    • Time to treatment response:
      • Mean: 12.2 mins83
      • Median: 10 (range 10-20) mins83
    • Time required to administer: 1.3-5 mins84
    • Advantages:
      • Less oronasopharyngeal and eye symptoms83
      • No refrigeration required for GlucaGen HypoKit® (can be kept up to 18 months at room temperature) or generic IM/ SC glucagon (stored at room temperature)85,86
    • Disadvantages:
      • Refrigeration required for GlucaGen® 85,86
      • Administration-related side effects (e.g., injection site pain and irritation)83
      • Other side effects: nausea, vomiting, vertigo83,84

IN = intranasal, IM = Intramuscular, G = generic, mg = milligram, SC = subcutaneous, T = trade

Troubleshooting common insulin situations

There are a number of situations that patients taking insulin should be aware of how to troubleshoot.

Select common insulin situation for details

  • Counsel patients as follows when they are sick (e.g., vomiting, diarrhea, fever, dehydration):
    • Monitor blood glucose more often (e.g., every 1-2 hours)
    • If at risk of dehydration (i.e., cannot keep food/liquid down), temporarily stop agents from the SADMANS list (see Type 2 diabetes and sick days: Medications to pause):
      • Secretagogues (e.g., gliclazide, glyburide, repaglinide)
      • ACE inhibitors
      • Diuretics, direct renin inhibitors
      • Metformin
      • ARBs
      • NSAIDS
      • SGLT2is
    • Adjust insulin amount depending on changes in food/liquid intake
    • When feeling better (i.e., able to eat/drink well), restart agents from the SADMANS list and regular insulin routine
  • Risk factors14
    • Type 1 diabetes (4.6-8 / 1,000 patient-years), type 2 diabetes (0.32-2 / 1,000 patient-years)88,89
    • New diabetes diagnosis
    • Non-adherence to insulin therapy
    • Severe infection
    • Surgery
    • Trauma
    • Myocardial infarction
    • Stroke
    • Thyrotoxicosis
    • Use of specific medications and drugs (e.g., SGLT2i, cocaine, atypical antipsychotics, interferon, diuretics, glucocorticoids, lithium)
    • Ultra low carb or keto diet
  • Pregnant patients
    • Pregnant patients in DKA typically present with lower blood glucose levels than non-pregnant patients
    • There are case reports of euglycemic DKA in pregnancy
  • Clinical presentation of DKA
    • Symptoms: Urge to breathe deeply, nausea, vomiting, abdominal pain, altered sensorium
    • Signs: Kussmaul respiration, acetone-odoured (fruity-smelling) breath
  • Clinical presentation of HHS

    • Symptoms: Polyuria, polydipsia, weakness
    • Signs: Extracellular fluid volume depletion, seizures, stroke-like state
  • Management of mild DKA at home (mild = alert; not drowsy, not in stupor or coma)14
    • In usual care, patients can self-manage early DKA if clinically stable and able to drink fluids
    • Monitor every 1-2 hours: blood glucose, nausea, vomiting, extreme thirst, ketones (with a reader/meter that accepts ketone strips, e.g., FreeStyle Libre®, FreeStyle Insulinx®, FreeStyle Precision Neo®)
  • Hospitalization14
    • For patients with clinical decline (and/or a positive ketone test), recommend an evaluation at the emergency department given the concern of a rapid clinical decline (patients should not drive themselves)
  • Encourage patients to participate in regular physical activity
  • Insulin dose adjustments may be needed due to physical activity
    • Exact insulin dose adjustments cannot be provided
    • Adjustments will range (e.g., minimal to 50%), depending on the type/duration of exercise and blood glucose levels
  • Counsel patients who plan to participate in physical activity:90,91
    • Monitor blood glucose before, during and a few hours after any physical activity
    • Adjust insulin as needed
    • Always carry rapid-acting carbohydrates (e.g., dextrose tablets)
    • Consider insulin timing when physical activity is planned
    • Avoid injecting insulin into subcutaneous tissue next to the primary muscle used (activity will increase insulin absorption)
    • Eat before before any physical activity
    • Ensure proper hydration and watch for signs and symptoms of dehydration (e.g., increased thirst, nausea, severe fatigue, blurred vision or headache)14
  • Risk
    • Diabetes, the use of insulin and its complications can affect driving performance.
    • Possible risks include: impaired sensory or motor function, impaired cognition, diabetic eye disease, nerve damage, kidney disease, cardiovascular disease, peripheral vascular disease, stroke and incidents of hypoglycemia14
  • Assessment
    • All drivers taking insulin should have fitness to drive assessed every 2 years14
    • Driver’s license may be suspended if a patient is determined unfit to drive or experiences an accident caused by hypoglycemia92
    • Medical professionals in Ontario have a legal obligation to report to the appropriate regulatory body patients who have conditions that impair their driving ability (see Reporting a driver for medical review).14,93
  • Counsel patients on insulin secretagogues and/or insulin to (see Drive safe with diabetes):14
    • Measure blood glucose levels immediately before driving (must be >4.0 mmol/L)
    • Re-test at least every 4 hours while driving
      • At least every 2 hours if the patient has a history of severe hypoglycemic episodes (e.g., loss of consciousness) or hypoglycemia unawareness (e.g., lack of early warning symptoms of hypoglycemia, such as tremor, sweatiness and palpitations)
    • If blood glucose <4.0 mmol/L, treat hypoglycemia (i.e., ingestion of 15g of carbohydrate). Re-test and wait 40 minutes after blood glucose returns to >4.0 mmol/L before driving
    • Eat next meal or snack (containing carbohydrate and protein) within an hour
    • Always keep an emergency supply of fast-acting carbohydrates (e.g., dextrose tablets) and a glucose monitoring system inside the vehicle
  • Commercial vehicle licensing14,92
    • Canadians with diabetes (with or without insulin) can be licensed to drive a commercial vehicle in Canada (and now the United States) if medical standards are met.
  • Presentation
    • Lipohypertrophic area(s) can develop under the skin where the same injection or infusion site is used repeatedly
    • Lipohypertrophy usually presents as thickened or rubbery lesions (can vary in size and shape).
    • Some lesions are easily seen (e.g., a large bulge), while others require detected by palpation (e.g., a hard lump) or ultrasound
  • Risk factors
    • Lipohypertrophy can develop from repeated use of the same area, reusing insulin needles, more frequent insulin injections, higher dose insulin and a lack of systematic rotation
  • Effect of insulin
    • Lipohypertrophy can decrease the rate of insulin absorption or make it more erratic/delayed, resulting in higher doses of insulin needed to achieve glycemic targets
  • Prevention
  • Treatment
    • Have patient avoid injecting in the site
    • Lipohypertrophy may take 3-6 months to reduce or resolve
  • Counsel patients
    • Night before surgery
      • Consider reducing long-acting, intermediate-acting or premixed insulin by 20-25%
      • Stop prandial (bolus) insulin when fasting begins
    • Morning of surgery (defer to any pre-op information patient has been given if available)
      • Patients on a twice-daily dosing of basal insulin should consider reducing the normal morning dose by 20%
      • If morning blood glucose > 6.7 mmol/L: reduce intermediate-acting or premixed insulin to 50% of the usual dose
      • If morning blood glucose < 6.7 mmol/L: do not take intermediate-acting or premixed insulin. This will minimize the risk of hypoglycemia

 

  • Glucocorticoid-induced hyperglycemia can occur in patients with or without diabetes
  • Monitoring
    • Monitor blood sugar three times daily
  • Indications to consider treatment
    • Blood glucose >12 mmol/L on two occasions within a 24-hour period (consider checking ketones if indicated)
  • Treatment options
    • If NOT on insulin: adding a sulfonylurea or adjusting current sulfonylurea dose may be considered. Insulin may be needed.
    • If ON insulin: adjust basal insulin daily (may need >30% increase)
    • Treatment considerations should be individualized based on glucocorticoid drug (e.g., prednisone has mid-day peak, dexamethasone is longer acting), treatment duration, and patient risks of hyperglycemia and hypoglycemia. A second opinion from a specialist may be considered (e.g., e-Consult)
    • Careful monitoring and subsequent decreases in antihyperglycemic therapy is prudent when steroid dose is tapered and/or when clinical status changes

Patient resources

Resources

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