MEDICAL PROTOCOL - INESSS · Revised version (October 2016): An expert committee of the Institut national d’excellence en santé et en services sociaux (INESSS). Effective date:

1 Medical Protocol - Diabetes | INESSS

MEDICAL PROTOCOL

Subject of this medical protocol:

Adjustment of hypoglycemic agents or insulin and laboratory tests for monitoring type 2 diabetes.

Validated by:

Original version (October 2013): The Comité d’experts ministériel sur les ordonnances collectives.

Revised version (October 2016): An expert committee of the Institut national d’excellence en santé et en services sociaux (INESSS).

Effective date:

October 2016

Reference:

Yes No

Adjustment of hypoglycemic agents or insulin and laboratory tests for monitoring type 2 diabetes (No.: ).

Approved by: INESSS Revision date:

April 2019

Expiry date:

October 2019

AUTHORIZED PROFESSIONALS

Nurses and pharmacists practicing their profession in Québec.

TARGETED CLINICAL CONDITIONS

Persons diagnosed with type 2 diabetes and referred by the treating physician for joint follow-up by an authorized professional.

OVERALL OBJECTIVES

To achieve the therapeutic target set by the treating physician.

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INESSS | Medical Protocol - Diabetes

INSTRUCTIONS

1. GLYCEMIC TARGETS

GLYCEMIC CONTROL TARGETS: GLYCATED HEMOGLOBIN (HbA1C)

HbA1c (%) Details

≤ 7% For most persons with type 2 diabetes.

≤ 6.5% For certain individuals, to further lower their risk of retinopathy and nephropathy. Benefit should be weighed against the risk of hypoglycemia.

7.1 to 8.5%

For certain individuals for whom less aggressive treatment is desired (limited life expectancy, high level of functional dependence, severe coronary artery disease associated with high risk of an ischemic event, multiple comorbidities, unnoticed hypoglycemic episodes, severe recurrent hypoglycemic episodes, longstanding diabetes and difficulty achieving an HbA1c level ≤ 7% despite effective doses of several hypoglycemic agents and the use of basal insulin, and frail, elderly persons).

GLYCEMIC CONTROL TARGETS: CAPILLARY BLOOD GLUCOSE LEVELS

Capillary blood glucose level

Details

4.0 to 7.0 mmol/L Preprandial (AC) *

5.0 to 10.0 mmol/L 2 hours postprandial (PC)

5.0 to 8.0 mmol/L 2 hours postprandial (PC): if the target HbA1c is not achieved

* Preprandial (AC) capillary blood glucose levels for frail, elderly persons: 5.0 to 12.0 mmol/L.

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Medical Protocol - Diabetes | INESSS

2. HYPOGLYCEMIC AGENTS

2.1 GENERAL PRINCIPLES

Therapeutic intent:

• HbA1C < 8.5%: if the targets are not achieved within 2 or 3 months with lifestyle management, metformin should be initiated.

• HbA1C ≥ 8.5% (with no metabolic decompensation): metformin should be initiated at the same time as lifestyle management. A combination of hypoglycemic agents may be considered.

• Symptomatic hyperglycemia (with metabolic decompensation): insulin should be initiated with or without metformin.

Combining hypoglycemic agents at submaximal doses helps achieve glycemic targets faster and with fewer adverse effects than monotherapy at the maximum dose.

When hypoglycemic agents are combined with or without insulin, classes with different mechanisms of action should be used.

All medication additions and adjustments, combined with lifestyle management, should make it possible to achieve glycemic targets within 3 to 6 months.

Adjustment principles:

Calculate the average capillary blood glucose level for each time of the day for the past 3 to 7 days.

Gradually increase the medication until:

• Preprandial capillary blood glucose levels < 7 mmol/L or < the targets set by the physician are obtained. • The occurrence of intolerance (e.g., gastrointestinal problems).

Modify the dose of only one hypoglycemic agent at a time.

Hypoglycemic and hyperglycemic episodes:

Correct hypoglycemic episodes first, starting with the first one of the day, before correcting hyperglycemic episodes.

Do not take into account a hypoglycemic or hyperglycemic episode associated with an exceptional or explainable one-time situation.

When adjusting hypoglycemic agents, return to the previous dose if intolerance or hypoglycemic episodes occur.

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2.2 GENERAL CONSIDERATIONS AND DOSAGE TITRATION REGIMENS

2.2.1 BIGUANIDES

GENERAL CONSIDERATIONS AND TITRATION REGIMENS FOR THE CLASS OF BIGUANIDES

Drug Starting dose * and

administration schedule

Titration regimen Details

METFORMIN Available strengths: 500 and 850 mg Scored tablets RAMQ: covered

250 to 500 mg PO BID at meals

Titration if BID administration: ↑ each dose by 250 mg every 1 to 2 weeks The daily dose can be split into 2 or 3 doses (BID or TID), depending on tolerance and compliance. Titration if TID administration: ↑ the dose by 250 mg (maximum: 2 doses/day) every 1 to 2 weeks. Maximum dose: 2550 mg/day If gastrointestinal intolerance: ↓ the dose to the lower adjustment step for 1 week or until symptom resolution. Resume with a slower dosage titration: ↑ the dose by 250 mg (maximum: 1 dose/day) or ↑ the adjustment interval.

Negligeable hypoglycemic episodes No weight gain Adverse effects: Gastrointestinal problems (e.g., nausea, diarrhea, abdominal cramps) Vitamin B12 deficiency Lactic acidosis: increased risk in the presence of conditions associated with hypoxemia and cardiovascular collapse Contraindications: Known drug allergy to biguanides History of lactic acidosis Severe renal failure: eGFR < 30 ml/min/1.73 m2 Severe liver failure Precautions: Radiological examination, surgery, severe dehydration: can exacerbate renal failure Pregnancy or breastfeeding Drug interactions: Drugs that can impair renal function (e.g., nonsteroidal anti-inflammatories (NSAIDs), antihypertensives, diuretics, iodine-containing contrast agents) Referral to physcian:

• Vitamin B12 deficiency • eGFR < 60 ml/min/1.73 m2

METFORMIN extended release Available strengths: 500 and 1000 mg Unscored tablets Not covered by the RAMQ

500 to 1000 mg PO daily at dinner

Titration: ↑ the dose by 500 mg every 1 to 2 weeks Maximum dose: 2000 mg/day If gastrointestinal intolerance: ↓ the dose to the lower adjustment level for 1 week or until symptom resolution before resuming the same dosage titration.

* Examples of usually prescribed starting doses.

LABORATORY TESTS

Tests Before the start of treatment * Every 3 months Every 6 months Once a year

HbA1c √ √ † √ ‡

CBC √

Vitamin B12 √

Creatinine (eGFR) √ √

* Tests accepted if performed within the past 3 months. † When the capillary blood glucose targets have not yet been achieved. ‡ When the capillary blood glucose targets are achieved.

http://www.ramq.gouv.qc.ca/fr/regie/publications-legales/Pages/liste-medicaments.aspx

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2.2.2 SECRETAGOGUES-SULFONYLUREAS

GENERAL CONSIDERATIONS AND DOSAGE TITRATION REGIMENS FOR THE CLASS OF SECRETAGOGUES-SULFONYLUREAS




GLICLAZIDE Extended release Available strengths: 30 and 60 mg 60 mg scored tablets 30 mg unscored tablets RAMQ codes

30 to 60 mg PO daily at breakfast or at the first main meal of the day

Titration: ↑ the dose by 30 mg every 2 weeks Maximum dose: 120 mg/day

Adverse effects: Weight gain Frequent hypoglycemic episodes (especially with glyburide). The risk is higher in the elderly and persons with renal failure. Contraindications: Known drug allergy to sulfonylureas Severe liver failure Renal failure:

Gliclazide, glimepiride: eGFR < 15 ml/min/1.73 m2 Glyburide: eGFR < 30 ml/min/1.73 m2

Precautions: Known drug allergy to sulfonamides Pregnancy or breastfeeding Drug interactions: Under the influence of sympatholytic drugs (e.g., β-blockers, clonidine), signs of adrenergic counter-regulation secondary to hypoglycemia may be ↓ or absent. GLP-1s and SGLT2s: risk of hypoglycemic episodes (a ↓ in the secretagogue dose is generally required, unless HbA1c > 8%) Referral to physician:

• Unexplainable hypoglycemic episodes: ↓ the dose to the lower adjustment step and advise the physician.

• Renal failure: Gliclazide and glimepiride: if eGFR < 30 ml/min/1.73 m2 Glyburide: if eGFR < 50 ml/min/1.73 m2

GLIMEPIRIDE Available strengths: 1, 2 and 4 mg RAMQ codes

1 mg PO daily at breakfast or at the first main meal of the day


2 mg PO daily at breakfast or at the first main meal of the day

Titration: ↑ the dose by 1 to 2 mg every 2 weeks Maximum dose: 8 mg/day

GLYBURIDE Available strengths: 2.5 and 5 mg Scored tablets RAMQ: covered

1.25 mg PO daily or BIDat meals If daily administration, give at the first main meal of the day

Titration: ↑ each dose by 1.25 mg every 2 weeks OR every 3 weeks in individuals ≥ 60 years of age The daily dose can be split into 2 doses (BID) if the AC capillary blood glucose levels at breakfast remain > 7 mmol/L. Maximum dose: 20 mg/day (maximum: 10 mg/dose)

2.5 to 5 mg PO daily or BID at meals If daily administration, give at the first main meal of the day

Titration: ↑ each dose by 2.5 mg every 2 weeks OR every 3 weeks in individuals ≥ 60 years of age The daily dose can be split into 2 doses (BID) if the AC capillary blood glucose levels at breakfast remain > 7 mmol/L. Maximum dose: 20 mg/day (maximum: 10 mg/dose)


LABORATORY TESTS


HbA1c √ √ † √ ‡



http://www.ramq.gouv.qc.ca/fr/professionnels/professionnels/Pages/codes-medicament-exception.aspx



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2.2.3 SECRETAGOGUES-MEGLITINIDES

GENERAL CONSIDERATIONS AND TITRATION REGIMENS FOR THE CLASS OF SECRETAGOGUES-MEGLITINIDES




REPAGLINIDE Available strengths: 0.5, 1 and 2 mg RAMQ codes

0.5 to 2 mg PO daily , BID or TID Administer before the meal (0 to 15 min before)

Titration: If the average mealtime capillary blood glucose level is high (˃ 7 mmol/L or > target set by the physician), double the dose that was given at the previous meal (maximum: 3 doses/day). Adjustment interval: every week. The daily dose can be split into 3 doses (TID). Maximum dose: 12 mg/day

Effect more pronounced on postprandial blood glucose levels Safe in the presence of renal failure Adverse effects: Hypoglycemic episodes Weight gain Headaches Constipation Contraindications: Known drug allergy to meglitinides Pregnancy or breastfeeding Liver failure Precautions: Do not take repaglinide if the meal is skipped Drug interactions: Clopidogrel: ↑ in the plasma repaglinide concentration (↑ risk of hypoglycemic episodes) GLP-1s and SGLT2s: risk of hypoglycemic episodes (a ↓ in the secretagogue dose is generally required, unless HbA1c > 8%) Referral to physician:

• Unexplainable hypoglycemic episodes: ↓ the dose to the lower adjustment step and advise the physician.


LABORATORY TESTS

Test Before the start of treatment * Every 3 months Every 6 months Once a year

HbA1c √ √ † √ ‡

* Test accepted if performed within the past 3 months. † When the capillary blood glucose targets have not yet been achieved. ‡ When the capillary blood glucose targets are achieved.


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2.2.4 ALPHA-GLUCOSIDASE INHIBITORS

GENERAL CONSIDERATIONS AND TITRATION REGIMENS FOR THE CLASS OF ALPHA-GLUCOSIDASE INHIBITORS




ACARBOSE Available strengths: 50 and 100 mg Scored tablets RAMQ: covered

25 mg PO daily, BID or TID at the start of the meal

Titration: the dose by 25 mg/day ( the dose for one meal at a time; maximum: 3 doses/day) every 2 weeks The daily dose can be split into 3 doses (TID). Maximum dose: 300 mg/day If gastrointestinal intolerance: ↓ the dose to the lower adjustment step for 1 week or until symptom resolution. Resume the titration, increasing the adjustment interval.

Negligible hypoglycemic episodes: if hypoglycemia occurs, do not give sucrose (p. ex., juice or white sugar), but rather honey or milk No weight gain Adverse effects: Gastrointestinal problems (e.g., diarrhea, flatulence, bloating) Contraindications: Known drug allergy to alpha-glucosidase inhibitors Pregnancy or breastfeeding Inflammatory bowel disease Intestinal obstruction Colonic ulcer Cirrhosis Renal failure: eGFR < 25 ml/min/1.73 m2 Referral to physician:

• eGFR < 25 ml/min/1.73 m2 • ↑ ALT (> 3 times the upper limit of normal

[ULN])


LABORATORY TESTS


HbA1c √ √ † √ ‡


ALT √ √

* Tests accepted if performed within the past 3 months. † When the capillary glycemic targets have not yet been achieved. ‡ When the capillary blood glucose targets are achieved.


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2.2.5 THIAZOLIDINEDIONES

GENERAL CONSIDERATIONS AND TITRATION REGIMENS FOR THE CLASS OF THIAZOLIDINEDIONES




PIOGLITAZONE Available strengths: 15, 30 and 45 mg RAMQ codes

15 mg PO daily In the morning


Negligible hypoglycemic episodes

Adverse effects: Weight gain Edema Bone fractures (ankles, wrists): especially in women during long-term use Contraindications: Known drug allergy to thiazolidinediones Pregnancy or breastfeeding Bladder cancer (active or past) Uninvestigated macroscopic hematuria Heart failure (New York Heart Association classes I to IV) or left ventricular dysfunction Severe liver failure Cirrhosis Peripheral edema Precautions: Atherosclerotic coronary artery disease (ASCAD) Osteoporosis Diabetic retinopathy Macular edema Perimenopause (can restore ovulation: in the risk of pregnancy) Drug interactions Insulin: risk of heart failure Pregabalin: additive fluid retention

Referral to physician:

• If weight gain > 3 kg in 2 weeks and presence of the following symptoms, withdraw the drug and advise the physician: lower-limb edema, dyspnea, unusual fatigue.

• eGFR < 30 ml/min/1.73 m2 • ↑ ALT (> 3 times the upper limit of normal

[ULN])


LABORATORY TESTS


HbA1c √ √ † √ ‡


ALT √ √



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2.2.6 GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS

GENERAL CONSIDERATIONS AND TITRATION REGIMENS FOR THE CLASS OF GLP-1S




ALBIGLUTIDE Available formats: Injectable solutions of 30 mg/0.5 ml and 50 mg/0.5 ml Not covered by the RAMQ

30 mg SC every week The administration schedule can be modified: respect a minimum of 72 hrs between doses.

Titration: ↑ the dose to 50 mg after 4 weeks Maximum dose: 50 mg/week If gastrointestinal intolerance: ↓ the dose to the lower adjustment step for 1 week or until symptom resolution. Resume the titration, increasing the adjustment interval.

Negligible hypoglycemic episodes Significant weight loss Adverse effects: Gastrointestinal problems (e.g., nausea, vomiting): effects ↓ after a few weeks in heart rate Injection site reaction Contraindications: Known drug allergy to GLP-1s Pregnancy or breastfeeding Personal or family history of medullary thyroid carcinoma Multiple endocrine neoplasia syndrome type 2 Renal failure:

Liraglutide: if eGFR < 30 ml/min/1.73 m2

Precautions: History of pancreatitis Liver failure Heart disease that could be exacerbated by an in the heart rate (e.g., congestive heart failure, atrial fibrillation, ischemic heart disease) Inflammatory heart disease Drug interactions Insulin or secretagogues: risk of hypoglycemic episodes (a ↓ in the insulin or secretagogue dose is generally required, unless HbA1c > 8%) Referral to physician:

• eGFR < 30 ml/min/1.73 m2

DULAGLUTIDE Available formats: Injectable solutions of 0.75 mg/0.5 ml and 1.5 mg/0.5 ml Exceptional medication

0.75 mg SC every week The administration schedule can be modified: respect a minimum of 72 hrs between doses.

Titration: ↑ the dose by 0.75 mg after 4 weeks Maximum dose: 1.5 mg/week If gastrointestinal intolerance: ↓ the dose to the lower adjustment step for 1 week or until symptom resolution. Resume the titration, increasing the adjustment interval.

LIRAGLUTIDE Available format: Injectable solution of 6 mg/ml Exceptional medication

0.6 mg SC daily If severe nausea, the dose can be administered at bedtime (HS).

Titration: ↑ the dose by 0.6 mg every 2 weeks Maximum dose: 1.8 mg/day If gastrointestinal intolerance: ↓ the dose to the lower adjustment step for 1 week or until symptom resolution. Resume the titration, increasing the adjustment interval.


LABORATORY TESTS


HbA1c √ √ † √ ‡





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2.2.7 SODIUM-GLUCOSE COTRANSPORTER TYPE-2 (SGLT2) INHIBITORS

GENERAL CONSIDERATIONS AND TITRATION REGIMENS FOR THE CLASS OF SGLT2s




CANAGLIFLOZIN Available strengths: 100 and 300 mg Unscored tablets Exceptional medication

100 mg PO daily in the morning

Titration: ↑ the dose to 300 mg after 4 weeks Maximum dose: 300 mg/day

Negligible hypoglycemic episodes Significant weight loss Adverse effects: Constipation Hypotension Urinary infection Genital yeast infection Pollakiuria Polyuria Contraindications: Known drug allergy to SGLT2s Pregnancy or breastfeeding Active or past bladder cancer (dapagliflozin) Renal failure:

Empagliflozin, canagliflozin: if eGFR < 45 ml/min/1.73 m2 Dapagliflozin: if eGFR < 60 ml/min/1.73 m2

Precautions: Dehydration: can alter renal function Drug interactions Digoxin (canagliflozin): ↑ in the plasma digoxin concentration Loop diuretics (especially furosemide): risk of volume depletion (a ↓ in the dose of the loop diuretic should be considered and blood pressure closely monitored) Antihypertensives: risk of hypotension (a ↓ in the antihypertensive dose should be considered and blood pressure closely monitored) Insulin and secretagogues: risk of hypoglycemic episodes (a ↓ in the insulin or secretagogue dose is generally required, unless HbA1c > 8%) Referral to physician:

• eGFR < 60 ml/min/1.73 m2

DAPAGLIFLOZIN Available strengths: 5 and 10 mg 5 mg unscored tablets Exceptional medication

5 mg PO daily Titration: ↑ the dose to 10 mg after 4 weeks Maximum dose: 10 mg/day

EMPAGLIFLOZIN Available strengths: 10 and 25 mg Exceptional medication

10 mg PO daily Titration: ↑ the dose to 25 mg after 4 weeks Maximum dose: 25 mg/day


LABORATORY TESTS


HbA1c √ √ † √ ‡






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3. INSULIN

3.1 GENERAL PRINCIPLES

Adjustment principles:

The adjustment should take into account the type of insulin, the administration schedule and the causes of hypoglycemic or hyperglycemic episodes.

Calculate, for each time of the day, the average capillary blood glucose level for the past 3 to 7 days.

It is best to adjust one type of insulin and correct one capillary blood glucose level at a time.

When insulin is used in combination, adjust the hypoglycemic agent first.

Opt for the maximum increase in the number of insulin units, unless there is a risk of hypoglycemic episodes.

Adjust insulin doses with considerable caution in elderly persons, given the increased risk of hypoglycemic episodes.

Hypoglycemic and hyperglycemic episodes:

Correct hypoglycemic episodes first, starting with the first one of the day, before correcting hyperglycemic episodes.

Do not take into account a hypoglycemic or hyperglycemic episode associated with an exceptional or explainable one-time situation. In the event of hypoglycemic episodes, adjust the insulin dose responsible (2 consecutive days at the same time of the day).

3.2 GENERAL CONSIDERATIONS

GENERAL CONSIDERATIONS REGARDING INSULIN

Drug Details

INSULIN Adverse effects: Frequent hypoglycemic episodes Significant weight gain Injection site reaction Contraindications: Known drug allergy to insulin Precautions: Pregnancy or breastfeeding: frequent dose adjustments required

Drug interactions: Thiazolidinediones: risk of heart failure Under the influence of sympatholytic drugs (e.g., β-blockers, clonidine), signs of adrenergic counter-regulation secondary to hypoglycemia may be ↓ or absent. GLP-1s and SGLT2s: risk of hypoglycemic episodes (a ↓ in the insulin dose is generally required, unless HbA1c > 8%)

LABORATORY TESTS

Test Before the start of treatment * Every 3 months Every 6 months Once a year

HbA1c √ √ † √ ‡

* Testaccepted if performed within the past 3 months. † When the capillary blood glucose targets have not yet been achieved. ‡ When the capillary blood glucose targets are achieved.

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3.3 TYPES OF INSULIN

INSULIN

Insulin Action Type of insulin Onset of

action Peak effect Duration of action

Administration schedule

Responsable for blood glucose level

BASA

L

Intermediate-acting

(RAMQ: covered)

Isophane (NPH)

1 to 3 hrs 5 to 8 hrs Up to

18 hrs

30 min before breakfast AC dinner blood glucose level

30 min before dinner

next-day AC breakfast blood glucose level

At bedtime next-day AC breakfast blood glucose level

Extended-action

analogues

(exceptional medications)

Detemir 90 min Not applicable 16 to 24 hrs At bedtime next-day AC breakfast blood

glucose level

Glargine 90 min Not applicable

Up to

24 hrs At bedtime next-day AC breakfast blood

glucose level

Glargine 300U Up to

6 hrs Not

applicable Up to

30 hrs At the same time

every day next-day AC breakfast blood

glucose level

PRAN

DIAL

Short-acting (RAMQ: covered)

Crystalline zinc (regular) 30 min 2 to 3 hrs 6.5 hrs 15 to 30 min

before a meal AC next-meal blood glucose level

Long-acting analogues

(RAMQ: covered)

Aspart 10 to 15 min 1 to 1.5 hrs 3 to 5 hrs 0 to 15 min

before breakfast

Pre-breakfast dose:

2-hr PC breakfast blood glucose level or AC lunch blood glucose

level *

Glulisine 10 to 15 min 1 to 1.5 hrs 3 to 5 hrs 0 to 15 min

before lunch

Pre-lunch dose:

2-hr PC lunch blood glucose level or AC dinner blood glucose level *

Lispro 10 to 15 min 1 to 2 hrs 3.5 to 4.75

hrs 0 to 15 min

before dinner

Pre- dinner dose:

2-hr PC dinner blood glucose level or HS blood glucose level *

PREM

IXED

(pra

ndia

l-bas

al)

Short/inter-mediate-

acting (RAMQ: covered)

Regular/NPH Depends on the prandial/basal ratio

15 to 30 min before breakfast

Pre-breakfast dose:

AC lunch blood glucose level and AC dinner blood glucose level

15 to 30 min before dinner

Pre-dinner dose:

HS blood glucose level and next-day AC breakfast blood glucose level

Rapid/inter-mediate-

acting analogues

(RAMQ codes)

Biphasic aspart Depends on the prandial/basal ratio 0 to 15 min before breakfast

Pre-breakfast dose:

2-hr PC breakfast blood glucose level or AC lunch blood glucose

level * and AC dinner blood glucose level

Lispro/lispro protamine Depends on the prandial/basal ratio 0 to 15 min

before dinner

Pre-dinner dose:

2-hr PC dinner blood glucose level or HS blood glucose level * and the

next-day AC breakfast blood glucose level

* If blood glucose level not determined 2 hours postprandially (PC).













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3.4 TITRATION REGIMENS

INSULIN TITRATION REGIMENS

ADJUSTMENT INTERVAL: EVERY 3 TO 7 DAYS

Time of day Capillary blood glucose level Adjustment * † Responsible insulin

NIGHT, BREAKFAST

Blood glucose level < 4 mmol/L or < glycemic targets

↓ the dose by 10% OR ↓ the dose by 2 to 4 units

Adjust the basal insulin administered at dinner or bedtime or the premixed insulin administered at dinner Blood glucose level > 7 mmol/L or > glycemic

targets and absence of nocturnal hypoglycemic episodes

↑ the dose by 10% OR ↑ the dose by 1 to 2 units (↑ the dose by 2 to 4 units if the blood glucose level ≥ 10 mmol/L)

LUNCHTIME



Adjust the prandial or premixed insulin administered at breakfast Blood glucose level > 7 mmol/L or > glycemic

targets ↑ the dose by 10% OR ↑ the dose by 1 to 2 units (↑ the dose by 2 to 4 units if the blood glucose level ≥ 10 mmol/L)

AFTERNOON (within 3 hrs after lunch)



Adjust the prandial insulin administered at lunchtime Blood glucose level > 7 mmol/L or > glycemic


DINNER (more than 3 hrs after dinner)



Adjust the basal or premixed insulin administered at breakfast or the prandial insulin administered at lunchtime

Blood glucose level > 7 mmol/L or > glycemic targets

↑ the dose by 10% OR ↑ the dose by 1 to 2 units (↑ the dose by 2 to 4 units if the blood glucose level ≥ 10 mmol/L)

BEDTIME



Adjust the prandial or premixed insulin administered at dinner Blood glucose level > 7 mmol/L or > glycemic


* Two insulin titration regimens: a) percentage of the insulin dose OR b) number of insulin units. † Round off the dose (minimum: 1 unit).

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DEVELOPMENT PROCESS

The development process is based on the triangulation of a number of data sources, including best clinical practice recommendations and both contextual and experiential data.

A systematic review of the clinical practice guideline literature, consensus reports and health technology assessment reports published between 2012 and 2016 was first conducted to identify recommendations concerning pharmacological treatment modalities for type 2 diabetes. Product monographs and Health Canada advisories were consulted as well. The methodology used to carry out this systematic literature review meets the production standards of the Institut national d’excellence en santé et en services sociaux (INESSS).

The analysis of the data from the systematic literature review was performed from a contextualization perspective regarding practice in Québec, using experiential data obtained from health professionals on an expert committee and the members of the INESSS project team.

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APPENDED A: HYPOGLYCEMIC AGENTS

HYPOGLYCEMIC AGENTS AVAILABLE IN CANADA

Biguanides Extended-release metformin Metformin

Secretagogues-sulfonylureas Chlorpropamide * Extended-release gliclazide Gliclazide * Glimepiride Glyburide Tolbutamide *

Secretagogues-meglitinides Repaglinide

Alpha-glucosidase inhibitors Acarbose

Thiazolidinediones Pioglitazone Rosiglitazone *

Dipeptidylpeptidase-4 (DPP-4) inhibitors Alogliptine † Linagliptine † Saxagliptine † Sitagliptine †

Glucagon-like peptide-1 (GLP-1) receptor agonists Albiglutide Dulaglutide Exenatide * Extented-release exenatide † Liraglutide

Sodium-glucose cotransportor type-2 (SGLT2) inhibitors Canagliflozine Dapagliflozine Empagliflozine

Combined formulations ‡ Alogliptin/metformin Alogliptin/pioglitazone Canagliflozin/metformin Dapagliflozin/metformin Empagliflozin/metformin

Linagliptine/metformine Rosiglitazone/glimepiride Rosiglitazone/metformin Saxagliptine/metformin Sitagliptine/metformin

* Used infrequently. † Fixed dose (no adjustment required) or adjustment made by the physician (based on the eGFR). ‡ The medical protocol targets individual formulations.

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ANNEXE B: ACRONYMS AND ABBREVIATIONS

AC preprandial

ALT alanine aminotransferase

ASCAD atherosclerotic coronary artery disease

BID twice daily

CBC complete blood count

DPP-4 dipeptidylpeptidase-4 inhibitor

e.g. for example

eGFR estimated glomerular filtration rate

GLP-1 glucagon-like peptide-1 receptor agonist

HbA1c glycated or glycosylated hemoglobin

HS at bedtime

NSAID nonsteroidal anti-inflammatory

PC postprandial

PO per os

RAMQ Régie de l’assurance maladie du Québec

SC subcutaneous

SGLT2 sodium-glucose cotransporter type 2 inhibitor

TID three times daily

ULN upper limit of normal

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Documents

MEDICAL PROTOCOL - INESSS · Revised version (October 2016): An expert committee of the Institut national d’excellence en santé et en services sociaux (INESSS). Effective date: