Type 2 Diabetes: Insulin Therapy

Last Updated: May 3, 2021

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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

Overview of insulin therapy for type 2 diabetes2

* Functionally dependent patients have a Clinical Frailty Scale8 score of 4-5 on a 9-point scale. Patients with frailty have a Clinical Frailty Scale8 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.9,10
† 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)3
  • 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)11,12
  • This dosing option is less flexible (requires a routine mealtime to prevent hypoglycemia) and offers less ability to correct for abnormal results11
Jump to: Premixed insulin options

Click on the sections below to get started:

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 day3
  • 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)2,24–26
      • Detemir and glargine 300 units/mL may lead to slightly less weight gain (≤1kg) than other options13,14
    • 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 correlation2,24–26
Cardiorenal outcomes
  • Insulin has a neutral effect on cardiorenal outcomes (safety but no risk reduction)1,2,18-20
Harms
  • Hypoglycemia
  • Lipohypertrophy
  • Local injection site reactions (exception: fewer with glargine vs. detemir)27
  • 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
  • Consider biosimilar insulin as it costs less – a biosimilar is a biologic drug that is highly similar to a biologic drug that was already authorized by Health Canada for sale33
  • Patients’ coverage (e.g., Ontario Drug Benefit [ODB], Non-Insured Health Benefits [NIHB]) plays into cost
Hypoglycemia risk (for basal insulin)21-23
  • 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 properties13-16

  • MortalityNot well studied (exception for prandial: studies have not shown a significant difference in mortality between rapid- and short-acting insulin)17
  • Quality of lifeNot well studied
  • Environmental impact of insulin
Consider the affordability of insulin
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Explore patient reimbursement opportunities for insulin related supplies
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Consider the environmental impact of insulin
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Insulin options

Basal insulin
Scroll (left-right) for details
  • Intermediate acting
    NPH (Humulin® N)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

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

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 5x3mL prefilled pens: $185
    • 5x3mL cartridges: $167
    • 10mL vial: $143

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 5x3mL prefilled pens: $127
    • 5x3mL cartridges: $114
    • 10mL vial: $89
    Comments
  • Intermediate acting
    NPH (Novolin® ge)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL prefilled pens
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 5x3mL prefilled pens: $167
    • 10mL vial: $143

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 5x3mL prefilled pens: $114
    • 10mL vial: $89
    Comments
  • Intermediate acting
    NPH pork (Hypurin®)

    100 units/mL

    Not on Ontario drug formulary

    Activity profile1

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

    Coverage28,29

    • ODB 𝙓
    • NIHB 𝙓

    Dosage forms28

    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 10mL vial: $584

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 10mL vial: $355
    Comments
  • Long-acting
    Degludec (Tresiba®)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL prefilled pens

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 5x3mL prefilled pens: $370

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 5x3mL prefilled pens: $250
    Comments
  • Long-acting
    Degludec (Tresiba®)

    200 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 3x3mL prefilled pens

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 3x3mL prefilled pens: $442

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 3x3mL prefilled pens: $298
    Comments
  • Long-acting
    Detemir (Levemir®)

    100 units/mL

    Activity profile1

    • Onset: 1.5h
    • Peak: Almost peakless
    • Duration: 6-24h

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL prefilled pens
    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 5x3mL prefilled pens: $370
    • 5x3mL cartridges: $367

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 5x3mL prefilled pens: $250
    • 5x3mL cartridges: $247
    Comments
  • Long-acting
    Glargine (BasaglarTM)

    100 units/mL

    Activity profile1

    • Onset: 1.5h
    • Peak: Almost peakless
    • Duration: 24h

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL prefilled pens
    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 5x3mL prefilled pens: $234
    • 5x3mL cartridges: $234

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 5x3mL prefilled pens: $159
    • 5x3mL cartridges: $159
    Comments
  • Long-acting
    Glargine (Lantus®)

    100 units/mL

    Activity profile1

    • Onset: 1.5h
    • Peak: Almost peakless
    • Duration: 24h

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

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

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 5x3mL prefilled pens: $310
    • 5x3mL cartridges: $310
    • 10mL vial: $209

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 5x3mL prefilled pens: $209
    • 5x3mL cartridges: $209
    • 10mL vial: $142
    Comments
  • Long-acting
    Glargine (Toujeo®)

    300 units/mL

    Activity profile1

    • Onset: 1.5h
    • Peak: No peak
    • Duration: Up to 36h

    Coverage28,29

    • ODB ✓
    • NIHB ✓ (only 1.5mL; 3mL not covered)

    Dosage forms28

    • 3×1.5mL or 5×1.5mL prefilled pens
    • 3x3mL or 2x3mL prefilled pens

    Cost for usual dose (50 units/day for 100 days supply; basal alone)*30

    • 3×1.5mL or 5×1.5mL prefilled pens: $323
    • 3x3mL or 2x3mL prefilled pens: $351

    Cost for usual dose (25 units/day for 100 days supply; basal + bolus; cost is for basal component)*30

    • 3×1.5mL or 5×1.5mL prefilled pens: $180
    • 3x3mL or 2x3mL prefilled pens:$180
    Comments

Prandial (bolus) insulin

Scroll (left-right) for details
  • Rapid-acting
    Aspart (Novorapid®)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    Dosage forms28

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

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $147
    • 5x3mL cartridges: $142
    • 10mL vial: $107
    Comments
  • Rapid-acting
    Aspart (Fiasp®)

    100 units/mL

    Not on Ontario drug formulary

    Activity profile1

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

    Coverage28,29

    • ODB 𝙓
    • NIHB 𝙓

    Dosage forms28

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

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $157
    • 5x3mL cartridges: $152
    • 10mL vial: $115
    Comments
  • Rapid-acting
    Glulisine (Apidra®)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

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

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $124
    • 5x3mL cartridges: $123
    • 10mL vial: $95
    Comments
  • Rapid-acting
    Lispro (Humalog®)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    Dosage forms28

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

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $138
    • 5x3mL cartridges: $139
    • 10mL vial: $107
    Comments
  • Rapid-acting
    Lispro (Admelog®)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB 𝙓

    Dosage forms28

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

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $112
    • 5x3mL cartridges: $112
    • 10mL vial: $87
    Comments
  • Rapid-acting
    Lispro (Humalog®)

    200 units/mL

    Activity profile1

    • Onset: 30-45 min
    • Peak: 0.75-2.5h
    • Duration: 3.5-4.75h

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL prefilled pens

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $129
    Comments
  • Short-acting
    Regular insulin (Humulin® R)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL cartridges: $115
    • 10mL vial: $89
    Comments
  • Short-acting
    Regular insulin (Novolin®ge Toronto)

    100 units/mL

    Activity profile1

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

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 5x3mL cartridges: $112
    • 10mL vial: $88
    Comments
  • Short-acting
    Regular insulin (Entuzity®)

    500 units/mL

    Not on Ontario drug formulary

    Activity profile1

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

    Coverage28,29

    • ODB 𝙓
    • NIHB 𝙓

    Dosage forms28

    • 2x3mL prefilled pens

    Cost for usual dose (25 units/day for 100 days supply)*30

    • 2x3mL prefilled pens: $120
    Comments

Premixed insulin and GLP1-RA + insulin combinations

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

    Dosage forms28

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL cartridges: $176
    • 10mL vial: $151
    Comments
  • Short-acting + intermediate-acting
    Premixed regular/NPH (Novolin®ge 30/70)

    100 units/mL

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL cartridges
    • 10mL vial

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL cartridges: $162
    • 10mL vial: $144
    Comments
  • Short-acting + intermediate-acting
    Premixed regular/NPH (Novolin®ge 40/60)

    100 units/mL

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL cartridges: $163
    Comments
  • Short-acting + intermediate-acting
    Premixed regular/NPH (Novolin®ge 50/50)

    100 units/mL

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL cartridges: $163
    Comments
  • Rapid-acting + intermediate-acting
    Aspart/aspart protamine suspension (Novomix® 30)

    100 units/mL

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL cartridges: $191
    Comments
  • Rapid-acting + intermediate-acting
    Lispro/lispro protamine suspension (Humalog® Mix25)

    100 units/mL

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL prefilled pens
    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $205
    • 5x3mL cartridges: $206
    Comments
  • Rapid-acting + intermediate-acting
    Lispro/lispro protamine suspension (Humalog® Mix50)

    100 units/mL

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL prefilled pens
    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL prefilled pens: $201
    • 5x3mL cartridges: $203
    Comments
  • GLP1-RA + insulin combinations (not premixed insulins)
    Degludec/liraglutide (Xultophy®)

    100 units/mL

    Not on Ontario drug formulary

    Coverage28,29

    • ODB 𝙓
    • NIHB 𝙓

    Dosage forms28

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL cartridges: $1,065
    Comments
  • GLP1-RA + insulin combinations (not premixed insulins)
    Glargine/lixisenatide (Soliqua®)

    100 units/mL

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

    • 5x3mL cartridges

    Cost for usual dose (50 units/day for 100 days supply)*30

    • 5x3mL cartridges: $624
    Comments

* 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, 𝙓 = 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 patients

  • 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 points
  • “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)48
  • 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 insulin49, 50

 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 good for up to 28 days (detemir and glargine 300 units/mL  are safe at room temperature for 42 days, and degludec is safe at room temperature for 56 days) – 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 use51 

  • 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)52
  • 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 tool48 for individualized timing)
  • Blood glucose levels in the middle of the night (1-2 times/month) to determine if they are experiencing nocturnal hypoglycemia54
  • Blood glucose at least 2 times/day to safely titrate premixed insulin3
Targets2,3

See Insulin prescription for examples53

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
Managing other medications when starting basal insulin
  • Stop thiazolidinediones (e.g., pioglitazone)
  • Reduce secretagogue (e.g., gliclazide, glyburide, repaglinide) ≥ 50%
  • Adjust other medications on a patient-by-patient basis11,56
  • Continue metformin, and if applicable, GLP1-RA, SGLT2i or DPP4i unless contraindicated
    • Metformin reduces insulin requirements, weight gain, morbidity and mortality2
Initiating and titrating flow chart

Managing other medications when starting prandial (blous) insulin
  • Stop sulfonylureas, meglitinides and fixed-ratio combinations2
  • Continue metformin, and if applicable, GLP1-RA, SGLT2i or DPP4i unless contraindicated
    • Metformin reduces insulin requirements, weight gain, morbidity and mortality2
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

Managing other medications when starting premixed/GLP1-RA+ insulin
  • Stop sulfonylureas (if on twice-daily premixed insulin), meglitinides, thiazolidinediones (e.g., pioglitazone) and duplicate insulins2,22
  • Consider dose reduction of agents other than metformin
  • Adjust other medications on a patient-by-patient basis11,56
  • Continue metformin, and if applicable, GLP1-RA, SGLT2i or DPP4i unless contraindicated
    • Metformin reduces insulin requirements, weight gain, morbidity and mortality2
Initiating and titrating flow chart

Switching Insulin

How to switch insulin11,22

  • 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’
Switch insulin using a 20% dose reduction11,22

Use this technique (unless otherwise specified) to minimize the risk of hypoglycemia

The insulin on the left may be switched to the insulin on the right using a 20% dose reduction (100 units/mL unless otherwise specified):

  • Basal insulin
    (twice daily dose)

    • Detemir (Levemir®)
    • Glargine (BasaglarTM, Lantus®)
    • NPH (Humulin® N, Novolin®ge)
  • Basal insulin
    (once daily dose)

    • Degludec (Tresiba®)
    • Glargine (BasaglarTM, Lantus®)
    • Glargine 300 units/mL (Toujeo®)
  • Degludec (Tresiba®)
  • Detemir (Levemir®)
  • Glargine (BasaglarTM, Lantus®)
  • Glargine 300 units/mL (Toujeo®)
  • (if >80 units/day, consider twice daily dosing)
  • Degludec (Tresiba®)
  • Detemir (Levemir®)
  • Glargine (BasaglarTM, Lantus®)
  • NPH (Humulin® N, Novolin®ge) (consider dividing to twice-daily dosing)
  • Glargine 300 units/mL (Toujeo®)
  • Degludec (Tresiba®)
  • Detemir (Levemir®)
  • Glargine (BasaglarTM, Lantus®)
Switch insulin ‘unit-to-unit’11,22

May be used for the following insulin (100 units/mL unless otherwise specified)

The insulin on the left may be switched to the insulin on the right ‘unit to unit’ (100 units/mL unless otherwise specified):

  • Basal insulin
    (once daily dose)​

  • Degludec (Tresiba®) (unless A1C ≤7%, then decrease dose by 20%)
  • Basal insulin

  • Premixed insulin (consider a dose 10-20% lower than existing basal and prandial doses)
  • Glargine (Basaglar™, Lantus®)

  • Glargine 300 units/mL (Toujeo®) (the starting dose can be the same but a higher daily dose may eventually be needed)
  • Glargine (Lantus®)
  • Glargine (BasaglarTM)
  • Lispro (Humalog®)
  • Lispro (Admelog®)
  • NPH (Humulin® N, Novolin®ge)
  • Degludec (Tresiba® 100 units/mL only)
  • Detemir (Levemir®)
  • Glargine (BasaglarTM, Lantus®)
  • (unless NPH twice-daily dose, then decrease dose by 20%)
  • Regular insulin (Humulin® R, Novolin®ge Toronto)
  • Aspart (Novorapid®, Fiasp®)
  • Glulisine (Apidra®)
  • Lispro (Humalog®, Admelog®)
  • >200 units/day of basal, prandial or premixed insulin
  • Regular insulin 500 units/mL (Entuzity®) (unless A1C ≤8%, then decrease dose by 20%)

Managing hypoglycemia

It is safer and more effective to prevent hypoglycemia than to t reat it after hypoglycemia occurs.8 Counsel patients who are at high-risk for hypoglycemia on how to prevent low blood glucose.3

Hypoglycemia is defined by:3
  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 symptoms3

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 system3
    • 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®)3
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 months3
Adjust medication
  • Consider using medication (see Type 2 diabetes: non-insulin pharmacotherapy)7 and insulin (e.g., long-acting insulin) with a lower risk of hypoglycemia3
  • 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)60
  • Adjust insulin regimen or ratio61

Risk factors for severe hypoglycemia

Patient risk factors
  • Advancing age and frailty3,62
  • Female gender63
  • Low A1C (<6.0%)3
  • Hypoglycemia unawareness3**
  • Prior episode of severe hypoglycemia3
  • Long duration of diabetes (insulin insufficiency)62
  • Neuropathy3
  • Renal impairment (for eGFR <30, consider adjusting insulin dose and timing to minimize insulin stacking)3, 62
  • Cognitive impairment3
  • Poor health literacy3
  • Food insecurity or erratic eating patterns3, 62
Medication risk factors
  • Use of insulin64
  • Long-term use of insulin therapy3
  • Basal insulin component too high64
  • Prandial (bolus) insulin doses not adjusted for physical activity, carbohydrate intake or skipped meals 62
  • Not adjusting medications after weight loss or withdrawal of medications that raise blood glucose (e.g., corticosteroids)62
  • 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)55
  • Lipohypertrophy59
  • Drugs that cause or mask symptoms of hypoglycemia (e.g., anti-hyperglycemics, beta blockers, ACE inhibitors, ethanol, fluoroquinolones, salicylates)65

**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.3

Range of hypoglycemia severity3

Treating hypoglycemia3

  • 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*)3
  2. Re-test blood glucose in 15 minutes. If the blood glucose level remains at <4.0 mmol/L, re-treat with another 15g carbohydrate3
  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 source3

*People taking an alpha glucosidase inhibitor (acarbose) must use glucose (dextrose) tablets or, if unavailable, milk or honey to treat hypoglycemia.3

Conscious patient

  1. Oral ingestion of 20g carbohydrate (glucose tablets or equivalent preferred*)3
  2. Re-test blood glucose in 15 minutes. If the blood glucose level remains at <4.0 mmol/L, re-treat with another 15g carbohydrate3
  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 source3

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)3,66
  2. Caregiver or support person should call for emergency services and notify the care team as soon as possible3
  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 source3

Unconscious patient (with intravenous access)

  1. Caregiver or support person should administer 10-25g (20–50 mL of D50W) glucose intravenously over 1-3 minutes3
  2. Caregiver or support person should call for emergency services and notify the care team as soon as possible3
  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 source3

*People taking an alpha glucosidase inhibitor (acarbose) must use glucose (dextrose) tablets or, if unavailable, milk or honey to treat hypoglycemia.3

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 carbohydrates3,66
  • Intranasal and intramuscular/subcutaneous glucagon are similarly effective. Some studies however, demonstrate that intramuscular/subcutaneous glucagon may be slightly more effective.67,68 Intranasal glucagon may be preferred due to ease of use, and intramuscular/subcutaneous glucagon may be preferred due to lower cost.69
Scroll (left-right) for details
  • Intranasal glucagon (Baqsimi®) 66

    Coverage28,29

    • ODB 𝙓
    • NIHB 𝙓

    Dosage forms28

    • 3mg prefilled device

    Usual dose

    • 3mg IN66

    Cost for usual dose

    • T: $165
    Comments
  • Intramuscular/ subcutaneous glucagon (GlucaGen®, GlucaGen HypoKit®)70,71

    Coverage28,29

    • ODB ✓
    • NIHB ✓

    Dosage forms28

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

    Usual dose

    • 1mg IM/SC70,71

    Cost for usual dose

    • G: $122
    • T: $124
    Comments

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 factors3
    • Type 1 diabetes (4.6-8 / 1,000 patient-years), type 2 diabetes (0.32-2 / 1,000 patient-years)73,74
    • 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)3
    • 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®)
  • Hospitalization3
    • 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:75,76
    • 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)3
  • 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 hypoglycemia3
  • Assessment
    • All drivers taking insulin should have fitness to drive assessed every 2 years3
    • Driver’s license may be suspended if a patient is determined unfit to drive or experiences an accident caused by hypoglycemia78
    • 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).3,77
  • Counsel patients on insulin secretagogues and/or insulin to (see Drive safe with diabetes):3
    • 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 licensing3,78
    • 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

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