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CADTH Health Technology Review
Authors; Daniel Trinh, and Matthew McDonald.
This Environmental Scan was conducted to document the current landscape in Canada of sodium-glucose cotransporter-2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus (T2DM), heart failure (HF), and chronic kidney disease (CKD) as well as glucagon-like peptide-1 (GLP-1) receptor agonists for T2DM and weight management. The scan focuses on the regulatory status, exclusivity status, and reimbursement status of these drugs across Canadian public formularies.
SGLT2 inhibitors have been an integral part of the management of T2DM. There are 3 SGLT2 inhibitors publicly reimbursed in Canada: dapagliflozin (Forxiga), canagliflozin (Invokana), and empagliflozin (Jardiance), with several fixed-dose combination drug products also available.1-5 SGLT2 inhibitors are an oral drug that reduce blood glucose concentrations by inhibiting the reabsorption of glucose in the kidney and facilitating the excretion of glucose in the urine.6 In addition to the glycemic benefits for T2DM, some SGLT2 inhibitors have been shown to have beneficial cardiovascular and renal effects in patients with overt atherosclerotic cardiovascular disease (CVD), HF, and CKD.7
GLP-1 receptor agonists are a newer class of drugs used in the treatment of T2DM. There are 12 brand products of GLP-1 receptor agonists approved by Health Canada: semaglutide (Ozempic, Rybelsus, Wegovy), liraglutide (Victoza, Saxenda), liraglutide–insulin degludec (Xultophy), dulaglutide (Trulicity), lixisenatide (Adlyxine), lixisenatide–insulin glargine (Soliqua), and exenatide (Byetta, Bydureon, Bydureon BCise). GLP-1 receptor agonists are primarily administered via injection or orally, and they increase the production of insulin while also inhibiting glucagon, a hormone responsible for increasing glucose production.8 In addition to the glycemic benefits of GLP-1 receptor agonists, some GLP-1 receptor agonists have shown benefits on weight management and potentially cardiovascular outcomes.
T2DM is a chronic condition characterized by high blood glucose levels resulting from insufficient insulin secretion or insulin resistance. It is estimated that more than 3 million people in Canada are living with diabetes, and approximately 90% of these people have T2DM.9 Untreated hyperglycemia can contribute to the development of retinopathy, neuropathy, nephropathy, and CVD. Initial treatment for T2DM focuses on controlling glycemic levels with metformin and lifestyle modifications.10 Metformin may or may not be used with insulin in the case of symptomatic hyperglycemia or metabolic decompensation. Lifestyle changes include diet, weight reduction, and exercise. If glycemic goals are not achieved with initial treatment, or in cases with contraindications, Diabetes Canada Clinical Practice Guidelines suggest second-line treatment options, including insulin secretagogues, insulins, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinediones, SGLT2 inhibitors, and GLP-1 receptor agonists.
A body mass index (BMI) of 25 kg/m2 to 30 kg/m2 is considered overweight, and a BMI of more than 30 kg/m2 is considered obese.11 The Canadian Task Force on Preventive Health Care has reported that 67% of men and 54% of women are living with overweight or obesity in Canada.12 Weight management is multifaceted and includes physical activity and behaviour modification. If BMI is 30 kg/m2 or greater or is 27 kg/m2 with at least 1 comorbidity, drug therapy can include semaglutide, orlistat, liraglutide, and the combination of naltrexone and bupropion.13
HF is a condition characterized by structural or functional impairment of ventricular filling or ejection of blood, resulting in the heart’s inability to maintain the metabolic demands of tissues and organs.14 Common symptoms of HF include dyspnea, fatigue, and edema. It is estimated that 750,000 people in Canada are living with HF.15 The goal of treatment is to reduce symptoms and slow the decline of heart function by reducing, stopping, or reversing the progression of the underlying cause. Pharmacological treatment of HF with reduced ejection fraction includes angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitors, beta-blockers, mineralocorticoid receptor antagonists, sacubitril-valsartan, ivabradine, and SGLT2 inhibitors.16,17
CKD is defined as abnormalities of kidney structure or function, which have been present for more than 3 months with implications for health.18 CKD is characterized based on cause, glomerular filtration rate (GFR), and albuminuria category. CKD is characterized by gradual reduction in kidney function and is estimated to affect approximately 10% of adults living in Canada.19 Decreased kidney function results in excess build up of fluid, electrolytes, and waste in the body. This leads to reduced quality of life and may result in kidney failure and death.20,21 Treatment aims to reduce the risk of progression of CKD to kidney failure.22 Pharmacological therapy for CKD may include ACEis, ARBs, and statins.23,24 More recently, SGLT2 inhibitors have also demonstrated benefits on renal outcomes in CKD.25
In 2018 and 2019, SGLT2 inhibitors were among the top 10 drug classes with the largest contribution to growth in public drug program spending in Canada.26 In 2019, SGLT2 inhibitors contributed to an increase of $61.5 million in total public program spending, 13.2% of the total program spending growth, and 40% of the annual growth rate. In addition, empagliflozin and semaglutide were in the top 10 list of drugs in 2021.27 Given that Health Canada indications for SGLT2 inhibitors and GLP-1 receptor agonists have expanded in recent years, both are expected to continue to contribute significantly to drug spending in Canada in the future. This Environmental Scan is to better understand the current reimbursement landscape of SGLT2 inhibitors in Canada for the treatment of T2DM, weight management, HF, and CKD.
The objectives of this Environmental Scan were to provide a summary of the following for SGLT2 inhibitors in the treatment of T2DM, HF, and CKD, as well as for GLP-1 receptor agonists for T2DM and weight management:
The components of the information presented in this scan are presented in Table 1.
A grey literature search was conducted on key resources, including the websites of Health Canada’s drug product database, patent register, and data protection register; CADTH website (CADTH Common Drug Review [CDR] records); Canadian public drug plan formulary databases; and clinicaltrials.gov database. No bibliographic literature searches were performed. The public drug plan and Health Canada databases were searched between in November 2023.
Some information presented in this report was not available in the public domain and was obtained through personal communication with members of the CADTH Formulary Working Group Health Technology Assessment (FWG-HTA) committee.28 In these cases, permission was obtained to publish this information in this report, and all details obtained through personal communication were referenced accordingly (Alka Bhalla, Pharmacist, Correctional Services Canada, Ottawa, ON: personal communication, Nov 16, 2023). Information from 4 federal public drug plans was included: NIHB, CSC, VAC, and CAF. Publicly reimbursed medications for residents of Nunavut and the Northwest Territories follow the coverage category and reimbursement criteria of the NIHB program.29,30
Components for Literature Screening and Information Gathering.
This Environmental Scan focused on the 3 current SGLT2 inhibitors publicly reimbursed in Canada: canagliflozin (Invokana), dapagliflozin (Forxiga), and empagliflozin (Jardiance), along with available fixed-dose combinations of these drugs. Other SGLT2 inhibitors were excluded from the report. Private payers and Quebec’s public drug program, the Régie de l’assurance maladie du Québec, were excluded. Although the clinical and economic basis for a CADTH reimbursement recommendation for SGLT2 inhibitors and GLP-1 receptor agonists are included in the report, this Environmental Scan did not assess the comparative clinical effectiveness or the relative cost-effectiveness of the drugs used in the treatment of patients with T2DM, HF, CKD, or weight loss. Thus, any conclusions or recommendations about the value of these medications or their place in therapy were outside of the scope of the Environmental Scan.
Health Canada has approved 6 SGLT2 inhibitors and fixed-dose combination products for the treatment of T2DM, including dapagliflozin, dapagliflozin-metformin, canagliflozin, canagliflozin-metformin, empagliflozin, and empagliflozin-metformin. Detailed regulatory information for SGLT2 inhibitors, including NOC dates, first marketed date, and their approved indications are presented in Appendix 1. Figure 1 shows the Health Canada approval timeline for SGLT2 inhibitors by marketed date as well as the NOC dates of their indication for T2DM, HF, and CKD.
All SGLT2 inhibitors (dapagliflozin, canagliflozin, empagliflozin) are indicated as monotherapy for T2DM, but only when metformin is ineffective or contraindicated. SGLT2 inhibitors may be used to improve glycemic control as an add-on therapy in adult patients when combined with metformin, a sulfonylurea, insulin, sitagliptin (dapagliflozin), pioglitazone (canagliflozin and empagliflozin), and linagliptin (empagliflozin). Drugs that combine SGLT2 inhibitors and metformin are indicated for T2DM in patients who are already treated with some combination of SGLT2 inhibitor, metformin, a sulfonylurea, insulin, sitagliptin (dapagliflozin), and pioglitazone (canagliflozin and empagliflozin). Dapagliflozin is also indicated as an adjunct to diet, exercise, and standard care therapy in patients with T2DM and cardiovascular risk factors or established CVD. Canagliflozin is also indicated as an adjunct to diet, exercise, and standard-of-care therapy in patients with T2DM and established CVD or diabetic nephropathy. Empagliflozin is also indicated as an adjunct to diet, exercise, and standard-of-care therapy in patients with T2DM and established CVD.
Health Canada has approved 2 SGLT2 inhibitors (dapagliflozin and empagliflozin) for the treatment of HF. Dapagliflozin is indicated for the treatment of HF with reduced ejection fraction to reduce the risk of cardiovascular death, hospitalization for HF, and urgent HF visit. Empagliflozin is indicated as an adjunct to standard-of-care therapy for the treatment of chronic HF.
The only SGLT2 inhibitor with a Health Canada indication for the treatment of CKD is dapagliflozin. Dapagliflozin is indicated to reduce the risk of estimated GFR (eGFR) decline, end-stage kidney disease, and cardiovascular and renal death.
Dapagliflozin is the only SGLT2 inhibitor that has a Health Canada indication for T2DM, HF, and CKD.
Fixed-dose combination drugs that comprise SGLT2 inhibitors and DPP-4 inhibitors are not currently on the Canadian market and will not be discussed further in this Environmental Scan.
Health Canada has noted that the safety and efficacy of SGLT2 inhibitors have not been established in the pediatric population, and therefore are not indicated for patients younger than 18 years. Higher rates of adverse reactions have also been found for the older patients and therefore SGLT2 inhibitors should be used with caution for patients aged 65 years or older.
Health Canada has approved 6 GLP-1 receptor agonists and fixed-dose combination products for the treatment of T2DM and weight management, including semaglutide, liraglutide, liraglutide–insulin degludec, dulaglutide, lixisenatide, and lixisenatide–insulin glargine. Detailed regulatory information for GLP-1 receptor agonists, including NOC dates, first marketed date, and their approved indications are presented in Appendix 2. Figure 2 shows the Health Canada approval timeline for GLP-1 receptor agonists by marketed date and NOC date.
The GLP-1 receptor agonist exenatide (Byetta, Bydureon, Bydureon BCise) is not currently on the Canadian market and will not be discussed further in this Environmental Scan.
Except for liraglutide, GLP-1 receptor agonists are not indicated for patients younger than 18 years, and Health Canada has noted that safety and efficacy have not been established in the pediatric population. Liraglutide (Victoza) is indicated for patients with T2DM who are 10 years or older as an adjunct to metformin with or without basal insulin when glycemic levels are not within target rang on maximal dose of metformin combined with diet and exercise. Another liraglutide (Saxenda) has been approved for use in pediatric patients 12 years and older. Health Canada has noted that GLP-1 receptor agonists should be used with caution in patients aged 65 years or older, because greater sensitivity cannot be ruled out.
Health Canada Approval Timeline for SGLT2 Inhibitors by Marketed Date and NOC Dates for T2DM, HF, and CKD Indications.
Exclusivity status is a function of patent and data protection. Patent protection is a 20-year period offered to innovative drugs from the date of filing that can be applied in various manners (e.g., chemical, change in use). Data protection regulations in Canada are governed by regulations under the Food and Drug Regulations published in 2006.31,32 These regulations provide data protection for an 8-year term with a possibility of adding 6 more months for submissions that include pediatric studies. During this time, only the owner or generator of preclinical and clinical trial data can use these data to obtain marketing authorization for drugs, effectively preventing a second-entry manufacturer from filing a submission for a copy of that innovative drug. Data protection begins from the time of issuance of NOC by Health Canada and when the drug is added to the Health Canada's Register of Innovative Drugs.31,32
Health Canada Approval Timeline for GLP-1 Receptor Agonists by Marketed Date and NOC Dates.
Exclusivity status for SGLTS inhibitors, including data protection expiry date and patent end date, is presented in Table 2. As of this Environmental Scan, data protection has ended for dapagliflozin and canagliflozin as well as their fixed-dose combination drugs with metformin. Data protection for empagliflozin and its fixed-dose combination drug with metformin has not expired. Patent end dates for all SGLT2 inhibitors have not expired. There are currently 2 generic dapagliflozin drugs under review at Health Canada. Similarly, 3 generic versions of canagliflozin, 8 generic versions of empagliflozin, and 1 generic version of empagliflozin-metformin were identified to be under review at Health Canada. Of the approved generic products, 15 dapagliflozin generic drugs have been already issued approval, 11 of which are currently marketed in Canada.
Exclusivity status for GLP-1 receptor agonists, including data protection expiry date and patent end date, can be found in Table 3. As of this Environmental Scan, data protection has ended for liraglutide as well as its fixed-dose combination with insulin degludec. Data protection has not expired for semaglutide, dulaglutide, lixisenatide, and lixisenatide–insulin glargine. Patent end dates for all GLP-1 receptor agonists have not expired. There is currently 1 generic version of liraglutide under review at Health Canada.
Status of Data Protection and Patent Expiry for SGLT2 Inhibitors.
Status of Data Protection and Patent Expiry for GLP-1 Receptor Agonists.
CADTH review status and CDEC or Formulary Management Expert Committee (FMEC) recommendations for SGLT2 inhibitors are presented in Table 4, and a summary of the CDEC or FMEC recommendations for patients with T2DM, HF, and CKD are presented in Appendix 3.
CDEC recommendations for SGLT2 inhibitors as treatment for T2DM is to list with clinical and/or conditions. Dapagliflozin is recommended to be added on to treatment for patients with T2DM who have inadequate glycemic control on metformin or a sulfonylurea, and for whom insulin is not an option. It is also recommended to be added on to treatment for patients with T2DM who have inadequate glycemic control on insulin with metformin or insulin without metformin when metformin is contraindicated or not tolerated. Canagliflozin and empagliflozin are recommended to be added on to metformin and a sulfonylurea for patients with T2DM and inadequate glycemic control on metformin and a sulfonylurea, and for whom insulin is not an option. The cost condition associated with the recommendations for dapagliflozin, canagliflozin, and empagliflozin is that the drug plan cost of treatment should not exceed the drug plan cost of treatment with the least costly option within the SGLT2 inhibitor and DPP-4 inhibitor classes.
SGLT2 inhibitor and metformin fixed-dose combination drugs for patients with T2DM are recommended to be reimbursed with clinical criteria and/or conditions for patients with T2DM (except for Invokamet XR). Dapagliflozin-metformin is recommended to be reimbursed for patients with T2DM who are already stabilized on therapy with dapagliflozin and metformin separately. These patients should also have inadequate glycemic control on metformin (or metformin and insulin), a contraindication or intolerance to a sulfonylurea, and insulin is not an option for them. Canagliflozin-metformin is recommended to be reimbursed for patients with T2DM who have inadequate glycemic control on metformin and a sulfonylurea, and for whom insulin is not an option, and who are already stabilized on treatment with canagliflozin and metformin separately. Empagliflozin-metformin is recommended to be reimbursed for patients with T2DM who are eligible to receive empagliflozin and metformin separately based on participating drug plan reimbursement criteria. For all 3 SGLT2 inhibitor and metformin fixed-dose combination drugs, the drug plan costs for the fixed-dose combination should not exceed the combined cost of the SGLT2 inhibitor and metformin administered separately.
CDEC also recommends that dapagliflozin and empagliflozin be reimbursed for HF with clinical criteria and/or conditions as an adjunct for standard-of-care therapy in adults with New York Heart Association (NYHA) class II and III heart failure. Standard-of-care therapies include beta-blockers, ACEis or ARBs, or a mineralocorticoid receptor antagonist. Empagliflozin should only be reimbursed if the price is less costly than dapagliflozin for the treatment of chronic HF.
Recently, FMEC recommended that dapagliflozin be reimbursed for CKD in patients who meet the diagnostic criteria for CKD (eGFR 25 mL/minute/1.73 m2 to 75 mL/minute/1.73 m2) with a urine albumin-to-creatinine ratio of 200 mg/g to 5,000 mg/g and treated with an ACEi or ARB at the maximum-tolerated dose.
CADTH Review Status and CDEC or FMEC Recommendation for SGLT2 Inhibitors.
CADTH review status and CDEC recommendations for GLP-1 receptor agonists are presented in Table 5, and summary of CDEC recommendations are presented in Appendix 4.
CDEC recommended not to list liraglutide (Victoza) as treatment for T2DM. For all other GLP-1 receptor agonists, CDEC recommendations for the treatment of T2DM is to reimburse with clinical criteria and/or conditions. Semaglutide (Ozempic) is recommended to be reimbursed for treatment with metformin when diet and exercise combined with metformin do not adequately control glycemic levels. It should not be reimbursed as add-on therapy to metformin and another antihyperglycemic drug. The cost for semaglutide should not exceed the least costly reimbursed drug that can be used when metformin alone cannot adequately control glycemic levels. Oral semaglutide (Rybelsus) is recommended to be reimbursed as an adjunct to diet and exercise in addition to metformin when glycemic control is not achieved with metformin alone or in addition to other antihyperglycemic agents. The drug plan cost of Rybelsus should not exceed the least costly treatment with GLP-1 receptor agonists, DPP-4 inhibitors, or SGLT2 inhibitors. CDEC recommended that dulaglutide be reimbursed for treatment in combination with metformin, or with metformin and sulfonylurea, as long as the drug plan cost does not exceed the least costly pharmacotherapy reimbursed in combination with metformin or metformin and a sulfonylurea. Lixisenatide is recommended as an adjunct to diet and exercise in addition to basal insulin with or without metformin if the drug plan cost for lixisenatide does not exceed the least costly pharmacotherapy reimbursed for basal insulin with or without metformin.
CADTH Review Status and CDEC Recommendation for GLP-1 Receptor Agonists.
Liraglutide–insulin degludec is recommended to be reimbursed for T2DM treatment as an adjunct to lifestyle changes in addition to metformin with or without sulfonylurea when these, combined with basal insulin, do not provide adequate control of glycemic levels. However, liraglutide–insulin degludec should be discontinued if glycemic control is not achieved at maximum dose (1.8 mg of liraglutide and 50 units of insulin degludec) after 26 weeks of treatment. Cost for this drug should also not exceed the least costly GLP-1 receptor agonist and least costly basal insulin administered separately or in combination. CDEC recommends that lixisenatide–insulin glargine be reimbursed for T2DM treatment as an adjunct to diet and exercise if the drug plan cost does not exceed the combined costs of lixisenatide and insulin glargine provided separately.
For weight management, CDEC recommendations for semaglutide (Wegovy) and liraglutide (Saxenda) are to do not reimburse.
The pCPA was formed in 2010 for public drug plans to work together when entering negotiations with manufacturers for pharmaceuticals from which, if successful, a letter of intent (LOI) was created. The LOI lists the terms and conditions for funding a drug and is used to create a product listing agreement between each participating member jurisdiction and the manufacturer.30
Information on the pCPA negotiation status of SGLT2 inhibitors for T2DM, HF, and CKD can be found in Table 6. All SGLT2 inhibitors and metformin fixed-dose combination drugs have concluded with a LOI for T2DM. Dapagliflozin is the only SGLT2 inhibitor to conclude with an LOI for HF, while empagliflozin is under active negotiation. No LOIs have been negotiated for the CKD indication.
Overview of the pCPA Negotiation Status of SGLT2 Inhibitors.
Table 7 shows the information on the pCPA negotiation status of GLP-1 receptor agonists for T2DM and weight management. Semaglutide (only Ozempic), lixisenatide, and lixisenatide–insulin glargine have concluded with a LOI for T2DM.
Overview of the pCPA Negotiation Status of GLP-1 Receptor Agonists.
The current process for formulary listings begins with an LOI, which leads to product listing agreements with individual drug plans. However, not all drugs achieve the LOI stage; when they do, not all LOIs lead to successful product listing agreements with jurisdictions. Some jurisdictions can choose to not participate in a negotiation, or formulary listings may take longer if the drug is not a priority.33
Public drug plans list prescription medicines according to specific coverage categories that can be broadly classified as a restricted or unrestricted benefit. Unrestricted benefit refers to drugs with usage that is not limited by clinical criteria requiring authorization before drug plan coverage. Depending on the public drug plan, this type of formulary benefit status (coverage category) is referred to as benefit, open benefit, standard benefit, general benefit, or regular benefit. Restricted benefit refers to drugs with usage limited by specific clinical criteria or to a defined patient subgroup. Depending on the public drug plan, this type of formulary benefit status is categorized under Special Authorization, Exceptional Access Program, Exceptional Drug Status or Exception Status Drug, Limited Use, Limited Coverage Drug, or Prior Authorization.34 The restricted benefit categories can be further classified by the following reimbursement processes:
Restricted Benefit – Active: Special Authorization or Limited Coverage Drug (British Columbia), Special Authorization (Alberta, New Brunswick, Newfoundland and Labrador, Prince Edward Island, VAC, CAF), Exceptional Drug Status or Exception Status drug (Saskatchewan, Manitoba, Nova Scotia, Yukon), Exceptional Access Program (Ontario), or limited use (NIHB). Application for public reimbursement with the required clinical details must be made by the authorized prescriber using established processes (e.g., use of specific authorization forms). Each request is subject to a medication review by staff responsible for claims adjudication for the public drug plan.35-48
Restricted Benefit – Passive: Limited Use (Ontario) and Benefit with Criteria Medications (CSC). In comparison with Restricted Benefit – Active, the use of specific authorization forms and a medication review is not a requirement. Rather, a Limited Use code (Ontario) or a Reason for Use code (CSC) must be specified in the prescription.48,49
The formulary listing status for SGLT2 inhibitors in each jurisdiction of interest are presented in Table 8.
Dapagliflozin is an unrestricted benefit in the following jurisdictions of Alberta, British Columbia, Manitoba, Ontario, New Brunswick, Nova Scotia, Newfoundland and Labrador, Prince Edward Island, VAC, CSC, and CAF. For patients with T2DM for whom insulin is not an option, Ontario’s therapeutic notes allows dapagliflozin to be added on to metformin when there is inadequate glycemic control on metformin and there is a contraindication or intolerance to sulfonylurea, or vice versa. For patients with NYHA class II and III HF, Ontario’s therapeutic notes allows dapagliflozin to be used as an adjunct to standard-of-care therapy, which includes beta-blockers, ACEis or ARBs, and an MRA.
Restricted benefit: In Saskatchewan, special access may be given to patients with T2DM whose glycemic levels are within the target range, or who are intolerant to, metformin and a sulfonylurea.
Restricted benefit: As an add-on therapy, Saskatchewan requires a reduced left ventricular ejection fraction less than or equal to 40% and NYHA class II or III HF symptoms. Standard therapy includes a stable dose of an ACEi or ARB, a beta-blocker, or an MRA.
Dapagliflozin-metformin is an unrestricted benefit in British Columbia, Ontario, NIHB, VAC, and CSC. Ontario’s therapeutic notes require patients with T2DM to be stabilized on therapy with individual components, to replace the individual components for patients who have inadequate glycemic control on metformin, a contraindication or intolerance to sulfonylurea, and for whom insulin is not an option.
Restricted benefit: Three drug plans (New Brunswick, Yukon, CAF) require patients to be stabilized on therapy with individual components. Nova Scotia requires the same criteria in addition to insulin not being an option for the patient. In Prince Edward Island, special access may be granted for the treatment of patients with T2DM when already stabilized on therapy with dapagliflozin, metformin, as well as a sulfonylurea, and for whom insulin is not an option. Special access may also be granted to patients with T2DM in Alberta with inadequate glycemic control on a sufficient trial of metformin who are intolerant to sulfonylurea, or vice versa, and for whom insulin is not an option. Saskatchewan requires patients with T2DM who do not have stable glucose levels, or who are intolerant to, metformin and a sulfonylurea. Similar criteria exist for Newfoundland and Labrador, provided patients are not using insulin. Manitoba requires the patient to be stabilized on therapy with the combination of metformin and dapagliflozin, linagliptin, saxagliptin, or sitagliptin as separate components.
Canagliflozin is an unrestricted benefit in Ontario, and with VAC, CAF, and CSC. Ontario’s therapeutic notes require that patients with T2DM on maximally tolerated doses of metformin have inadequate glycemic control (hemoglobin A1c > 0.07) and either a contraindication or intolerance to sulfonylurea, or on maximal doses of sulfonylurea and for whom insulin is not an option.
Restricted benefit: Three drug plans (Saskatchewan, New Brunswick, NIHB) require that the patient be inadequately controlled on, or intolerant to, metformin and a sulfonylurea. As an add-on therapy, Newfoundland and Labrador requires intolerance to and/or inadequate glycemic control on metformin and sulfonylurea in patients not using insulin. Similarly, as an add-on therapy, 5 jurisdictions (Alberta, Manitoba, Nova Scotia, Prince Edward Island, Yukon) require intolerance to and/or inadequate glycemic control on metformin and sulfonylurea for those whom insulin in not an option.
Canagliflozin-metformin (only Invokamet) is an unrestricted benefit for CSC Health Services.
Restricted benefit: Canagliflozin-metformin is not a benefit in the jurisdictions included in this Environmental Scan, except for CSC Health Services and CAF. CAF requires stabilization on therapy with canagliflozin and metformin as separate components.
Empagliflozin is an unrestricted benefit in Ontario, NIHB, VAC, CSC, and CAF. Ontario’s therapeutic notes require that patients with T2DM on maximally tolerated doses of metformin have inadequate glycemic control (hemoglobin A1c > 0.07) and either a contraindication or intolerance to sulfonylurea, or on maximal doses of sulfonylurea and for whom insulin is not an option. In patients with T2DM and established CVD who have inadequate glycemic control (hemoglobin A1c > 0.07) after an adequate trial of metformin, Ontario also allows empagliflozin to be used as an adjunct to diet, exercise, and standard-of-care therapy to reduce cardiovascular death.
Restricted benefit: British Columbia requires inadequate glycemic control on the maximum-tolerated dose of metformin. Saskatchewan requires that glycemic control in patients with T2DM are not adequately controlled on, or are intolerant to, metformin and a sulfonylurea. Yukon requires that glycemic control in patients with T2DM are not adequately on maximum-tolerated doses of dual therapy of metformin and a sulfonylurea, or metformin and insulin. As an add-on therapy, for patients not using insulin Newfoundland and Labrador requires inadequate glycemic control on metformin and a sulfonylurea. Similarly, as an add-on therapy, 3 drug plans (Alberta, Nova Scotia, Prince Edward Island) require inadequate glycemic control on metformin and a sulfonylurea for those for whom insulin is not an option. As an add-on to metformin and a sulfonylurea, New Brunswick requires inadequate glycemic control on metformin and a sulfonylurea.
Restricted benefit: Eight drug plans (Alberta, Saskatchewan, Manitoba, New Brunswick, Nova Scotia, Prince Edward Island, Yukon, Newfoundland and Labrador) allow special authorization to patients with T2DM and established CVDs who have inadequate glycemic control on metformin for empagliflozin to reduce the incidence of cardiovascular death.
Empagliflozin-metformin is an unrestricted benefit in Ontario, NIHB, VAC, and CSC. Ontario’s therapeutic notes require that patients with T2DM on maximally tolerated doses of metformin have inadequate glycemic control (hemoglobin A1c > 0.07) and either a contraindication or intolerance to sulfonylurea, or on maximal doses of sulfonylurea and for whom insulin is not an option. In patients with T2DM and established CVD who have inadequate glycemic control (hemoglobin A1c > 0.07) after an adequate trial of metformin, Ontario also allows empagliflozin-metformin to be used as an adjunct to diet, exercise, and standard-of-care therapy to reduce CV death.
Restricted benefit: British Columbia provides special authorization in patients that have inadequate glycemic control on the maximum-tolerated dose of metformin. Saskatchewan requires that patients are not adequately controlled on, or are intolerant to, metformin and a sulfonylurea. Alberta requires patients have intolerance to and/or inadequate glycemic control on metformin and a sulfonylurea, and in whom insulin is not an option. Similarly, Newfoundland and Labrador require patients have intolerance to and/or inadequate glycemic control on metformin and a sulfonylurea and are not using insulin. Six drug plans (Manitoba, New Brunswick, Nova Scotia, Prince Edward Island, Yukon, CAF) allow special authorization in patients stabilized on therapy with empagliflozin and metformin as separate components.
Restricted benefit: Alberta and Saskatchewan allow special authorization to patients with T2DM and established CVDs who have inadequate glycemic control on metformin to reduce the incidence of cardiovascular death.
The formulary listing status for GLP-1 receptor agonists in each jurisdiction of interest are presented in Table 9.
Overview of Listing Status for SGLT2 Inhibitors for T2DM.
Overview of Listing Status for GLP-1 Receptor Agonists.
Ozempic is an unrestricted benefit in Ontario, NIHB, and VAC. Ontario’s therapeutic notes allow for the addition of Ozempic in combination with metformin and a sulfonylurea when diet and exercise with metformin and a sulfonylurea does not adequately control glycemic levels.
Restricted benefit: As add-on therapy for patients with T2DM, British Columbia and CSC require intolerance, contraindication, or inadequate glycemic control on a trial of metformin. Alberta requires patients with T2DM to have a contraindication, intolerance to, and/or inadequate glycemic control on a sufficient trial of metformin and a sulfonylurea, and for whom insulin is not an option. Six drug plans (Saskatchewan, Manitoba, Nova Scotia, Prince Edward Island, Newfoundland and Labrador, Yukon) allow access as an add-on to metformin and a sulfonylurea when this dual therapy with diet and exercise do not achieve adequate glycemic control. New Brunswick allows access as an add-on to metformin or metformin and a sulfonylurea when patients with T2DM have inadequate control on metformin or metformin and a sulfonylurea. CAF requires patients with T2DM have inadequate glycemic control after a trial of metformin and DPP-4 inhibitor, and metformin plus an SGLT2 inhibitor.
Restricted benefit: Rybelsus is not a benefit in any of the jurisdictions included in this Environmental Scan.
Restricted benefit: Wegovy is not a benefit in any of the jurisdictions included in this Environmental Scan.
Victoza is an unrestricted benefit in Nova Scotia.
Restricted benefit: Victoza is not a benefit in any of the jurisdictions included in this Environmental Scan.
Restricted benefit: Saxenda is not a benefit in any of the jurisdictions included in this Environmental Scan.
Restricted benefit: Liraglutide–insulin degludec is not a benefit in any of the jurisdictions included in this Environmental Scan.
Restricted benefit: Dulaglutide is not a benefit in any of the jurisdictions included in this Environmental Scan.
Lixisenatide is an unrestricted benefit in Ontario, NIHB, and VAC. Ontario’s therapeutic notes allow for the addition of lixisenatide to metformin and 1 of sulfonylurea, pioglitazone, or basal insulin when glycemic control is not achieved by diet and exercise with dual therapy.
Restricted benefit: Two drug plans (New Brunswick and Nova Scotia) allow lixisenatide to be added to basal insulin or basal insulin and metformin in patients with T2DM who have inadequate glycemic control on basal insulin or basal insulin and metformin. Alberta allows access as add-on therapy for treatment of T2DM in patients with contraindication to, intolerance to, and/or inadequate glycemic control on a trial of metformin, a sulfonylurea, and insulin. Saskatchewan and Manitoba allow lixisenatide to be combined with a basal insulin with or without metformin when patients with T2DM have inadequate glycemic control on, or intolerance to, metformin and a sulfonylurea. Newfoundland and Labrador allow the combination of lixisenatide with metformin and a sulfonylurea when diet and exercise plus metformin and a sulfonylurea do not achieve adequate glycemic levels.
Lixisenatide–insulin glargine is an unrestricted benefit in Ontario, NIHB, and VAC. Ontario’s therapeutic notes allows for lixisenatide–insulin glargine to be added to diet and exercise when glycemic levels are not adequately controlled on basal insulin (less than 60 units daily) in combination with metformin.
Restricted benefit: Saskatchewan and Manitoba allow lixisenatide–insulin glargine to be added to a basal insulin (less than 60 units per day) for adequate glycemic control in patients with T2DM. Newfoundland and Labrador allows access to lixisenatide–insulin glargine as an adjunct to diet and exercise when glycemic levels are inadequately controlled on basal insulin (60 units per day) in combination with metformin.
As SGLT2 inhibitors and GLP-1 receptor agonists have matured, Health Canada indications have expanded. With the entry of dapagliflozin generics in Canada, some public drug programs have made dapagliflozin an unrestricted benefit with reimbursement not limited by clinical criteria. Semaglutide is the GLP-1 receptor agonist reimbursed by most public drug programs in Canada, with most jurisdictions requiring specific clinical criteria to be met for reimbursement. With the expiration of data protection for SGLT2 inhibitors, the emergence of additional generics outside of dapagliflozin are expected.
angiotensin-converting enzyme inhibitor
angiotensin II receptor blocker
Canadian Armed Forces
Canadian Drug Expert Committee
chronic kidney disease
Correctional Service of Canada
cardiovascular disease
dipeptidyl peptidase-4
estimated glomerular filtration rate
Formulary Management Expert Committee
glomerular filtration rate
glucagon-like peptide-1
heart failure
Letter of Intent
Non-Insured Health Benefits
Notice of Compliance
New York Heart Association
pan-Canadian Pharmaceutical Alliance
sodium-glucose cotransporter-2
type 2 diabetes mellitus
Veterans Affairs Canada
Acknowledgement: Jennifer Horton
Overview of Regulatory Information for SGLT2 Inhibitors.
Overview of Regulatory Information for GLP-1 Receptor Agonists.
Summary of CDEC Recommendations for SGLT2 Inhibitors in Patients With T2DM.
Summary of CDEC Recommendations for SGLT2 Inhibitors in Patients With HF.
Summary of CDEC and FMEC Recommendations for SGLT2 Inhibitors in Patients With CKD.
Summary of CDEC Recommendations for GLP-1 Receptor Agonists.
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