Type 2 Diabetes: Non-Insulin Pharmacotherapy

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This tool is designed to support primary care providers to prescribe and manage non-insulin pharmacotherapy for adult patients living with type 2 diabetes. This is an update of the original Achieving glycemic control in type 2 diabetes tool, released in 2012.

Diagnostic criteria for diabetes

  • Fasting plasma glucose (FPG) ≥7.0 mmol/L*; OR
  • A1C ≥6.5%; OR
  • 2-hour plasma glucose (2hPG) in a 75g oral glucose tolerance test (OGTT) ≥11.1 mmol/L; OR
  • Random plasma glucose (PG) ≥11.1 mmol/L

* = fasting – no caloric intake for at least 8 hours
† = using a standardized, validated assay in the absence of factors that affect the accuracy of the A1C
‡ = random – anytime of the day, without regard to the interval since the last meal

Diagnosis of diabetes is confirmed if:
  • Symptomatic hyperglycemia is present (therefore confirmatory tests are not required); OR
  • The results of two laboratory tests are in the diabetes range (in the absence of symptomatic hyperglycemia)
    • The second confirmatory laboratory test must be done on another day, and it is preferable that the same test be repeated for confirmation (in a timely fashion, based on clinical judgment), with the exception of random PG.
Factors that affect A1C:
  • Factors that can increase A1C: iron deficiency, B12 deficiency, $ erythropoiesis, alcoholism, chronic renal failure, splenectomy
  • Factors that can decrease A1C: use of erythropoietin, iron or B12, reticulocytosis, chronic liver disease, ingestion of acetylsalicylic acid, vitamin C/E, decreased erythrocyte lifespan (e.g., chronic renal failure, hemoglobinopathies, splenomegaly, rheumatoid arthritis, antiretrovirals, ribavirin, dapsone)

A1C targets and considerations for glycemic control New

Individualize (and reassess) targets considering potential benefits and harms to the patient, and according to each patient’s:

  • Age and/or frailty
  • Comorbidities
  • Prognosis
  • Duration of diabetes
  • Risk of hypoglycemia
  • Patient preferences resources and support system number
  • Complexity and burden of medications

 

 

A1C targets

Some adults:
If easy/safe to achieve, without hypoglycemia (e.g., with lifestyle modification and metformin). In others, risks of an A1C of ≤6.5% may warrant deintensification of therapy.3,5

“Most” adults:
Guidelines differ on the target recommended for “most” adults, however they consistently note the need to individualize treatment intensity and therapy based on patient factors. To achieve A1C ≤ 7.0%, target:

  • FPG 4.0–7.0 mmol/L and/or
  • PPG 5.0–10.0 mmol/L or if A1C not at target, aim for PPG 5.0–8.0 mmol/L

HOWEVER, this must be balanced against the risk of hypoglycemia.

Functionally dependent adults (Clinical Frailty Scale11 score = 4-5, on a 9 point scale):

Deintensification (e.g., reducing dose, discontinuation) of therapy in older, frail adults is often appropriate to reduce potential harms (e.g., hypoglycemia, risk of polypharmacy, lack of time-to-benefit).

Adults with cardiovascular disease/risk:
Patients with A1Cs in the range of 7.3-7.9% have demonstrated reductions in cardiovascular, renal, and/or mortality outcomes. However studies featured a specific drug (an SGLT2i, GLP1-RA, or metformin) and demographic, rather than merely the intensity of glycemic control.6-10

Frail older adults (Clinical Frailty Scale11 score = 6-8, on a 9 point scale) and/or adults with dementia, limited life expectancy or a history of recurrent severe hypoglycemia and/or hypoglycemia unawareness.

Note: A1C tends to rise over time, even for patients on stable treatments.

Management of hyperglycemia in type 2 diabetes New

Non-insulin pharmacotherapy New

Shared decision-making

Shared decision-making is an approach to clinical decision-making in which patients and providers jointly consider clinical factors and patient preferences to arrive at a mutually agreeable decision.14 Shared decision-making aims to bridge the information gap between patients and providers while prioritizing patient autonomy.14

Engage patients in a discussion regarding which of the following factors are most important to them:15,16

Use this information and a shared decision-making approach to support patients in deciding which diabetes therapy they would prefer.

cost Affordability of therapy for 100 day supply
  • Green = < $100
  • Yellow = $100-$400
  • Red = > $400
IV Avoiding therapy that requires injections
  • Yellow = weekly injection
  • Red = daily injection
cost Avoiding therapy that increases risk of hypoglycemia
  • Red = risk of hypoglycemia
Heart Therapy that provides cardiovascular benefits
  • Green = cardiovascular benefit
  • Red = cardiovascular risk (e.g., worsening MI or heart failure)
cost Therapy that fits with daily routine
  • Green = twice daily or less administration
  • Yellow = ranges from once daily to 3+ daily
  • Red = 3+ administration per day, inconvenient
cost Avoiding therapy that has gastrointestinal side effects
  • Red = gastrointestinal side effects are common
weight Therapy that impacts weight change
  • Green = decreases weight
  • Red = increases weight
Lung Therapy that provides kidney protection
  • Green = provides kidney protection
  • Red = may cause acute renal injury

Non-insulin pharmacotherapy

First line options

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  • Biguanides
    Metformin HCL / Glucophage®
    Agent with evidence-based outcome benefits

    Generic available

    Formulations: 500mg tab and 850mg tab

    Coverage: 500mg tab ODB 𝙓  NIHB✓; 850mg NIHB✓

    A1C reduction (%)12,18: 1.0

    Dose18: Initial: 250–500mg po daily cc; Usual: 1000mg po bid cc OR 1700mg cc am and 850mg cc pm; Max: 2550mg daily OR 850mg tid

    Renal dose12,18: eGFR 30-45mL/min (≤1000mg daily); eGFR <30mL/min (avoid*)
    *Sometimes used at low dose when eGFR between 15-30 mL/min in renally stable patients

    Drug cost for usual dose* ($/100 days)17:
    Generic: $20 (1g bid) to $80 (850mg tid); Trade: $140

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments
  • Biguanides
    Metformin HCL / Glumetza®
    Agent with evidence-based outcome benefits

    Generic available

    Formulations: 500mg extended release tab and 1000mg extended release tab

    Coverage: ODB 𝙓  NIHB 𝙓

    A1C reduction (%)12,18: 1.0

    Dose18: Initial: 250–500mg po daily cc; Usual: 11000–2000mg po cc pm; Max: 2550mg daily

    Renal dose12,18: eGFR 30-45mL/min (≤1000mg daily); eGFR <30mL/min (avoid*)
    *Sometimes used at low dose when eGFR between 15-30 mL/min in renally stable patients

    Drug cost for usual dose* ($/100 days)17:
    Generic: $120 (1g/d) to $235 (2g/d); Trade: $300 (2g/d)

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Second line options

  • Avoid combining Dipeptidyl peptidase-4 inhibitor (DPP4i) with Glucagon-like peptide-1 receptor agonists (GLP1-RA).
  • Insulin secretagogues – sulfonylureas: Risk of hypoglycemia: gliclazide < glimepiride < glyburide
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  • Alpha-glucosidase inhibitor
    Acarbose / Glucobay®

    Generic available

    Formulations: 50mg tab and 100mg tab

    Coverage: ODB✓ (LU 175, 176) NIHB ✓ 

    A1C reduction (%)12,18: 0.7-0.8

    Dose18: Initial: 25mg po daily cc; Usual: 50–100mg po tid cc; Max: 100mg po tid cc

    Renal dose12,18: eGFR<25-30mL/min (contraindication)

    Drug cost for usual dose* ($/100 days)17:
    Generic: $74 to $100

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  • DPP4i
    Alogliptin / Nesina®

    NOT on Ontario drug formulary

    Formulations23: 6.25mg tab, 12.5mg tab, 25mg tab

    Coverage: ODB 𝙓 NIHB 𝙓

    A1C reduction (%)12,18: 0.5–0.7

    Dose18: 25mg po daily

    Renal dose12,18: eGFR 30-50mL/min (12.5mg po daily); eGFR <30mL/min (6.25mg po daily)

    Drug cost for usual dose* ($/100 days)17: Trade: $265

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  • DPP4i
    Linagliptin / Trajenta®

    Formulations: 5mg tab

    Coverage: ODB ✓ NIHB✓

    A1C reduction (%)12,18: 0.5–0.7

    Dose18: 5mg po daily

    Renal dose12,18:  eGFR <15mL/min (use with caution). No dosage adjustment.

    Drug cost for usual dose* ($/100 days)17: Trade: $297

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  • DPP4i
    Saxagliptin / Onglyza®

    Formulations: 2.5mg tab and 5mg tab

    Coverage: ODB ✓ NIHB ✓

    A1C reduction (%)12,18: 0.5–0.7

    Dose18: 5mg po daily

    Renal dose12,18:  eGFR <50mL/min (2.5mg po daily) eGFR <15mL/min (use alternative agent)

    Drug cost for usual dose* ($/100 days)17: Trade: $337

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  • DPP4i
    Sitagliptin / Januvia®

    Formulations: 25mg tab, 50mg tab, 100mg tab

    Coverage: ODB ✓ NIHB ✓ (for patients who did not achieve glycemic control or who demonstrated intolerance to an adequate trial of metformin and a sulfonylurea)

    A1C reduction (%)12,18: 0.5–0.7

    Dose18: 100mg po daily

    Renal dose12,18:  eGFR 30-49mL/min (50mg po daily); eGFR <30mL/min, hemodialysis, peritoneal dialysis, chronic kidney disease (25mg po daily)

    Drug cost for usual dose* ($/100 days)17: Trade: $354

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  • GLP1-RA – short acting
    Exenatide / Byetta®
    A

    NOT on Ontario drug formulary

    Formulations24: Pre-filled pen (multiuse) 250μg/mL, 1.2mL, 2.4mL Pk

    Coverage: ODB 𝙓 NIHB 𝙓

    A1C reduction (%)12,18: 0.6-1.4

    Dose18: Initial/Usual: 5μg SC bid ac, prior to main meals ≥6 hour apart; Max: 10μg SC bid ac

    Renal dose12,18: eGFR <50mL/ min (caution), <30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Trade: $510

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments
  • GLP1-RA – short acting
    Lixisenatide / Adlyxine®
    A

    Formulations24: Pre-filled pen (multiuse) 0.05mg/mL, 0.1mg/mL; 3mL Pk

    Coverage:  ODB ✓ NIHB ✓

    A1C reduction (%)12,18: 0.6-1.4

    Dose18: Initial: 10mcg SC daily ac x 2 weeks; Usual/Max: 20mcg SC daily ac

    Renal dose12,18: eGFR <15-20mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Trade: $419

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  • GLP1-RA – longer acting
    Dulaglutide / Trulicity®
    Agent with evidence-based outcome benefits

    NOT on Ontario drug formulary

    Formulations25: Pre-filled pen(single use) 0.75mg/0.5ml; 1.5mg/0.5ml

    Coverage: ODB 𝙓  NIHB 𝙓

    A1C reduction (%)12,18: 0.6-1.4

    Dose18: Initial: 0.75mg SC once weekly; Usual/Max: 1.5mg SC once weekly

    Renal dose12,18: eGFR <15mL/min (caution)

    Drug cost for usual dose* ($/100 days)17: Trade: $720 (12 weeks)

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  • GLP1-RA – longer acting
    Exenatide / Bydureon®

    NOT on Ontario drug formulary

    Formulations26: ER pen (powder, single use) 2mg

    Coverage: ODB 𝙓  NIHB 𝙓

    A1C reduction (%)12,18: 0.6-1.4

    Dose18: 2mg SC once weekly (must reconstitute)

    Renal dose12,18: eGFR <50mL/min (caution), <30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Trade: $775 (12 weeks)

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  • GLP1-RA – longer acting
    Liraglutide / Victoza®
    Agent with evidence-based outcome benefits

    NOT on Ontario drug formulary

    Formulations27: Pre-filled pen (multiuse): 6mg/mL; 3mL Pk

    Coverage: ODB 𝙓  NIHB 𝙓

    A1C reduction (%)12,18: 0.6-1.4

    Dose18: Initial: 0.6mg SC daily; Usual: After ≥1 week, increase 1.2mg SC daily x 1 week, then 1.8mg SC daily; Max: 1.8mg/d

    Renal dose12,18: eGFR <15-30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Trade : $1095 (1.8mg SC daily x 100 days)

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments
  • GLP1-RA – longer acting
    Liraglutide / Saxenda®

    Formulations27: Pre-filled 6mg/mL, Pen 5x3mL

    Coverage: ODB 𝙓  NIHB 𝙓

    A1C reduction (%)12,18: 0.6-1.4

    Dose18: Initial: 0.6mg SC daily; Usual:After ≥1 week, increase 1.2mg SC daily x 1 week, then 1.8mg SC daily x 1 week, then 2.4mg SC daily x 1 week, then 3.0mg; Max: 3.0mg/d

    Renal dose12,18: eGFR <15-30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Trade : $1095 (1.8mg SC daily x 100 days)

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments
  • GLP1-RA – longer acting
    Semaglutide / Ozempic®
    Agent with evidence-based outcome benefits

    Formulations: Pre-filled pen (multiuse): 1.34mg/mL; 1.5mL, 3mL Pk

    Coverage: ODB ✓ NIHB ✓

    A1C reduction (%)12,18: 1.5-2.010

    Dose18: Initial: 0.25mg SC once weekly; Usual: After ≥4 weeks increase 0.5mg SC once weekly x 4 weeks, then titrate up to 1mg SC weekly as tolerated; Max: 1mg SC once weekly

    Renal dose12,18: eGFR <30mL/min (caution)

    Drug cost for usual dose* ($/100 days)17: Trade : $390-$772

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments
  • GLP1-RA – longer acting
    Semaglutide / Rybelsus®
    Agent with evidence-based outcome benefits

    NOT on Ontario drug formulary

    Formulations28: Tab: 3mg, 7mg, 14mg

    Coverage: ODB 𝙓  NIHB 𝙓

    A1C reduction (%)12,18: 1.1

    Dose18: Initial: 3mg po daily 30 mins ac; Usual: After 30 days increase 7mg daily 30 mins ac; Max: 14mg daily

    Renal dose12,18: Not studied in eGFR < 30mL/min

    Drug cost for usual dose* ($/100 days)17: Trade : $818

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  • Insulin secretagogues – meglitinides
    Repaglinide / Gluconorm®

    Generic available

    Formulations28: Tab: 0.5mg, 1mg, 2mg

    Coverage: ODB 𝙓 EAP29 NIHB ✓

    A1C reduction (%)12,18: 0.7-1.1

    Dose18: Initial: A1C <8% 0.5mg po tid ac, A1C ≥8% 1-2mg po tid ac; Usual: 1-4mg po bidqid ac; Max: 16mg daily

    Renal dose12,18:eGFR <30mL/min (caution)

    Drug cost for usual dose* ($/100 days)17: Generic: $79-$167

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments
  • Insulin secretagogues – sulfonylureas
    Gliclazide / Diamicron MR®

    Generic available

    Formulations28: SR tab: 30mg; ER tab: 60mg

    Coverage: ODB ✓ NIHB ✓

    A1C reduction (%)12,18: 0.6-1.2

    Dose18: Initial: 30mg MR po daily; Usual: 60mg MR daily; Max: 120mg MR daily

    Renal dose12,18: eGFR <30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Generic: $16; Trade: $37

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  • Insulin secretagogues – sulfonylureas
    Gliclazide / Diamicron®

    Generic available

    Formulations28: Tab: 80mg

    Coverage: ODB ✓ NIHB ✓

    A1C reduction (%)12,18: 0.6-1.2

    Dose18: Initial: 40-80mg po daily in am cc; Usual: 80mg bid cc; Max: 160mg bid cc

    Renal dose12,18: eGFR <30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Generic: $29; Trade: $94

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  • Insulin secretagogues – sulfonylureas
    Glimepiride / Amaryl®

    Generic available

    Formulations28: Tab: 1mg, 2mg, 4mg

    Coverage:  ODB 𝙓 NIHB 𝙓

    A1C reduction (%)12,18: 0.6-1.2

    Dose18: Initial: 1-2mg po daily in am cc; Usual: 1-4mg po daily in am cc; Max: 8mg po daily cc

    Renal dose12,18: eGFR <30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Generic: $62

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  • Insulin secretagogues – sulfonylureas
    Glimepiride / Diabeta®

    Generic available

    Formulations28: Tab: 2.5mg, 5mg

    Coverage: ODB ✓ NIHB 𝙓

    A1C reduction (%)12,18: 0.6-1.2

    Dose18: Initial: 1.25-2.5 mg po daily cc; Usual: 5mg daily bid cc; Max: 10mg bid cc

    Renal dose12,18: eGFR <60 (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Generic: $15; Trade: $37

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments
  • SGLT2i or gliflozins
    Canagliflozin / Invokana®
    Agent with evidence-based outcome benefits

    Formulations28: Tab: 100mg, 300mg

    Coverage: ODB ✓ NIHB ✓ LU (for patients who did not achieve glycemic control or who demonstrated intolerance to an adequate trial of metformin and a sulfonylurea)

    A1C reduction (%)12,18: 0.5-0.7

    Dose18: Initial/Usual: 100mg po od daily am; Max: 300mg daily

    Renal dose12,18: eGFR <60mL/min (max dose 100mg daily); eGFR <60mL/min + UGT inducer (avoid); eGFR <45mL/min (caution); eGFR <30mL/min (contraindicated

    Drug cost for usual dose* ($/100 days)17: Trade: $321

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  • SGLT2i or gliflozins
    Dapagliflozin / Forxiga®
    Agent with evidence-based outcome benefits

    Formulations28: 5mg, 10mg

    Coverage: ODB ✓ NIHB ✓

    A1C reduction (%)12,18: 0.5-0.7

    Dose18: Initial/Usual: 5mg po daily am; Max: 10mg po daily am

    Renal dose12,18: eGFR < 45mL/min (not recommended); eGFR <30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Trade: $304

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  • SGLT2i or gliflozins
    Empagliflozin / Jardiance®
    Agent with evidence-based outcome benefits

    Formulations28: Tab: 10mg, 25mg

    Coverage: ODB ✓ NIHB ✓

    A1C reduction (%)12,18: 0.5-0.7

    Dose18: Initial/Usual: 10mg po daily am; Max: 25mg po daily am

    Renal dose12,18: eGFR <60mL/min (caution); eGFR <30mL/min (contraindicated)

    Drug cost for usual dose* ($/100 days)17: Trade: $304

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  • TZD
    Pioglitazone HCL / Actos®

    Generic available

    Formulations28: Tab: 15mg, 30mg, 45mg

    Coverage: ODB 𝙓 EAP29; NIHB ✓

    A1C reduction (%)12,18: 0.7-0.9

    Dose18: Initial: 15mg daily po daily; Usual: 30-45mg po daily; Max: 45mg po daily

    Renal dose12,18: eGFR <60mL/min (caution)

    Drug cost for usual dose* ($/100 days)17: Generic: $247–$366; Trade:$388-$578

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  • TZD
    Rosiglitazone / Avandia®

    Generic available

    Formulations: Tab: 2mg, 4mg, 8mg

    Coverage:  EAP29; ODB 𝙓 NIHB 𝙓

    A1C reduction (%)12,18: 0.7-0.9

    Dose18: Initial: 4mg po daily; Usual: 4mg po daily to bid; Max: 8mg po daily

    Renal dose12,18: eGFR <60mL/min (caution)

    Drug cost for usual dose* ($/100 days)17: Generic: $207; Trade: $292

    View benefits and CVD outcome, weight, harms and hypoglycemic risk, and comments

Combination products

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  • Insulin degludec/liraglutide (Xultophy®)

    Formulation17: 100 units/mL insulin degludec, 3.6mg/mL

    Usual dose18: 16 units/0.58mg – 50 units/1.8mg SC daily (50 units insulin daily)

    Coverage: ODB 𝙓17 or NIHB 𝙓19

    Drug cost for usual dose* ($/100 days)17: Trade: $370 for 5x3mL

  • Insulin glargine/lixisenatide (Soliqua®)

    Formulation17: 100U/mL, 33mcg/mL

    Usual dose18: 15 units/5mcg – 60 units/20mcg; SC daily (60 units insulin daily)

    Coverage: ODB ✓ NIHB ✓

    Drug cost for usual dose* ($/100 days)17: Trade: $215

  • Linagliptin/empagliflozin (Glyxambi®)

    Not on Ontario drug formulary

    Formulation17: Tab: 5/10mg, 5/25mg31

    Usual dose18: 1 tab po daily

    Coverage: ODB 𝙓 NIHB 𝙓

    Drug cost for usual dose* ($/100 days)17: Trade: $563

  • Metformin/canagliflozin (Invokamet®)

    Not on Ontario drug formulary

    Formulation17: Tab: 500/50mg, 850/50mg, 1000/50mg, 500/150mg, 850,150mg, 1000/150mg32

    Usual dose18: 1 tab po bid cc

    Coverage: ODB 𝙓 NIHB 𝙓

    Drug cost for usual dose* ($/100 days)17: Trade: $386

  • Metformin/dapagliflozin (Xigduo®)

    Formulation17: Tab: 850/5mg, 1000/5mg

    Usual dose18: 1 tab po bid cc

    Coverage: ODB ✓ NIHB ✓

    Drug cost for usual dose* ($/100 days)17: Trade: $273

  • Metformin/empagliflozin (Synjardy®)

    Formulation17: Tab: 500/5mg, 850/5mg, 1000/5mg, 500/12.5mg, 850/12.5mg, 1000/12.5mg

    Usual dose18: 1 tab po bid cc

    Coverage: ODB ✓ NIHB ✓

    Drug cost for usual dose* ($/100 days)17: Trade: $307

  • Metformin/linagliptin (Jentadueto®)

    Formulation17: Tab: 500/2.5mg, 850/2.5mg, 1000/2.5mg

    Usual dose18: 1 tab po bid cc

    Coverage: ODB ✓ NIHB ✓

    Drug cost for usual dose* ($/100 days)17: Trade: $311

  • Metformin/saxagliptin (Komboglyze®)

    Formulation17: Tab: 500/2.5mg, 850/2.5mg, 1000/2.5mg33

    Usual dose18: 1 tab po bid cc

    Coverage: ODB ✓ NIHB ✓

    Drug cost for usual dose* ($/100 days)17: Trade: $283

  • Metformin/sitagliptin (Janumet®)

    Formulation17: Tab: 500/50mg, 850/50mg, 1000/50mg

    Usual dose18: 1 tab po bid cc

    Coverage: ODB ✓ NIHB ✓

    Drug cost for usual dose* ($/100 days)17: Trade: $383

  • Metformin/sitagliptin (Janumet XR®)

    Formulation17: ER tab: 500/50mg, 1000/50mg, 1000/100mg

    Usual dose18: 1-2 tab(s) po once daily cc

    Coverage: ODB ✓ NIHB ✓ LU (for patients who did not achieve glycemic control or who demonstrated intolerance to an adequate trial of metformin and a sulfonylurea)

    Drug cost for usual dose* ($/100 days)17: Trade: $196-$383

DPP4i: Dipeptidyl peptidase-4 inhibitors; GLP1-RA: Glucagon-like peptide-1 receptor agonists; SGLT2i: Sodium-glucose cotransporter-2 inhibitors; TZD: Thiazolidinediones
underlined text: important information, *= prices reflect cost to consumer and include markup and dispensing fee, = weight neutral, ac = before meals, AE = adverse events, BG = blood glucose, bid = twice daily, cc = with meal, CrCl = creatinine clearance, CV = cardiovascular, CVD = cardiovascular disease, EAP = Exceptional Access Program, eGFR = estimated glomerular filtration rate, ER = extended release, GI = gastrointestinal, HCL = hydrochloric acid, HDL-C = high density lipoprotein cholesterol, HF = heart failure, LDL-C = low density lipoprotein cholesterol, LFTs = liver function tests, LU = limited use, MACE = major adverse cardiovascular event, max = maximum, MI = myocardial infarction, μg = microgram, mg = milligram, mL = milliliter, MR = modified release, NIHB = non-insured health benefits for First Nations and Inuit, ODB = Ontario Drug Benefit, po = by mouth, qid = four times daily, SC = subcutaneous, SCr = serum creatinine, SR = sustained release, Tab = tablets, tid = three times daily, UGT = UDP-glucuronosyltransferase

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