Summary
Recently added to the growing spectrum of diabetes mellitus drugs, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and glucagon-like peptide-1 (GLP-1) agonists are generally used to supplement treatment with metformin. This Environmental Scan presents the current reimbursement statuses of these medications by publicly funded drug plans in Canada.
Unlike fixed-dose combination (FDC) products containing biguanides or other drugs, single-drug products of DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists are often reimbursed by jurisdictions; however, their listing statuses vary from full benefit (FB) to limited use (LU) or exceptional use (EU). In contrast, many FDC products are non-benefit (NB) drugs. While the criteria for LU and EU vary between the drug classes, they are often similar across jurisdictions. The criteria essentially aim to reimburse these medications only after an unsuccessful trial of metformin and/or a sulfonylurea. The criteria also consider other parameters when insulin is not an option, such as renal function or the presence of cardiovascular (CV) risk factors; these parameters may vary depending on the jurisdiction.
Context
Diabetes mellitus is a chronic condition that results when the body produces insufficient amounts of insulin (type 1 diabetes) or is unable to use the insulin it produces (type 2 diabetes).1 Diabetes mellitus can lead to major complications, such as CV disease, vision loss, and end-stage renal disease.2,3 In 2015, it was estimated that 3.4 million Canadians (9.3%) suffered from diabetes mellitus; of these, 90% had type 2 diabetes (T2D).
First-line therapy used in patients with T2D is metformin monotherapy.4 When metformin is contraindicated or not tolerated, or when treatment goals are not achieved after three months of use at the maximum tolerated dose, other options need to be considered.4 Other therapies include: orlistat, alpha-1 glucosidase inhibitors, meglitinides, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 agonists, or insulin.4
Recent guidelines recommend DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists as supplemental treatment to metformin. Their selection would account for patient characteristics as well as the cost of therapy.4 There are certain clinical situations that may warrant the use of these drugs as second-line therapy (for example, patients with a history of CV disease), as there is emerging evidence supporting such use in this population. In particular, a number of CV outcomes trials (CVOTs) have recently been completed or are close to completion. For example, three completed CVOTs (CANVAS, EMPA-REG OUTCOME, and LEADER) reported CV benefits for SGLT-2 inhibitors canagliflozin and empagliflozin and for the GLP-1 agonist, liraglutide.4 Similarly, in the May 2017 CADTH Recommendations Report on second-line therapy for T2D, the CADTH Canadian Expert Drug Committee (CDEC) recommended that adults with T2D and established CV disease consider therapy based on CDEC recommendations for individual T2D drugs that have been reviewed specifically for the CV indication by CADTH Common Drug Review (CDR).5 At the time this report was prepared, the reimbursement of empagliflozin was endorsed by CDEC for patients at high risk of CV events;5; submissions for CV indication had not been received for the other drugs with CV benefit. As evidence continues to emerge, the way newer drugs for T2D are reimbursed and prescribed may evolve.
This Environmental Scan aims to determine the current reimbursement statuses of DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists available in Canada (Table 1).
Table 1: Drugs of Interest
| Drug Class | Drug | Brand Name | Manufacturer |
|---|---|---|---|
| Single-Drug Products (Oral) | |||
| DPP-4 inhibitors | alogliptin | Nesina | Takeda Canada Inc. |
| linagliptin | Trajenta | Boehringer Ingelheim Canada Ltd. | |
| saxagliptin | Onglyza | AstraZeneca Canada Inc. | |
| sitagliptin | Januvia | Merck Canada Inc. | |
| SGLT-2 inhibitors | canagliflozin | Invokana | Janssen Inc. |
| dapagliflozin | Forxiga | AstraZeneca Canada Inc. | |
| empagliflozin | Jardiance | Boehringer Ingelheim Canada Ltd. | |
| ertugliflozin | Steglatro | Merck Canada Inc. | |
| Single-Drug Products (Injectable) | |||
| GLP-1 agonists | dulaglutide | Trulicity | Eli Lilly Canada Inc. |
| exenatide, exenatide ER | Byetta, Bydureon | AstraZeneca Canada Inc. | |
| liraglutide | Victoza | Novo Nordisk Canada Inc. | |
| lixisenatide | Adlyxine | Sanofi Aventis Canada Inc. | |
| semaglutide | Ozempic | Novo Nordisk Canada Inc. | |
| Fixed-Dose Combination Drug Products (Oral) | |||
| DPP-4 inhibitors/ biguanides | alogliptin/metformin | Kazano | Takeda Canada Inc. |
| linagliptin/metformin | Jentadueto | Boehringer Ingelheim Canada Ltd. | |
| saxagliptin/metformin | Komboglyze | AstraZeneca Canada Inc. | |
| sitagliptin/metformin | Janumet, Janumet XR | Merck Canada Inc. | |
| SGLT-2 inhibitors/ biguanides | canagliflozin/metformin | Invokamet | Janssen Inc. |
| dapagliflozin/metformin | Xigduo | AstraZeneca Canada Inc. | |
| empagliflozin/metformin | Synjardy | Boehringer Ingelheim Canada Ltd. | |
| ertugliflozin/metformin | Segluromet | Merck Canada Inc. | |
| SGLT-2 inhibitors/ DPP-4 inhibitors | dapagliflozin/saxagliptin | Qtern | AstraZeneca Canada Inc. |
| empagliflozin/linagliptin | Glyxambi | Boehringer Ingelheim Canada Ltd. | |
| ertugliflozin/sitagliptin | Steglujan | Merck Canada Inc. | |
| Fixed-Dose Combination Drug Products (Injectable) | |||
| GLP-1 agonists/ insulin | liraglutide/insulin degludec | Xultophy | Novo Nordisk Canada Inc. |
| lixisenatide/insulin glargine | Soliqua | Sanofi Aventis Canada Inc. | |
DPP-4 = dipeptidyl peptidase-4; GLP-1 = glucagon-like peptide-1; SGLT-2 = sodium-glucose cotransporter-2; XR = extended release.
Objectives
The objective of this Environmental Scan is to identify and summarize information regarding the respective reimbursement statuses of drugs pertaining to DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists by provincial, territorial, and federal drug plans in Canada.
Methods
The information in this report was gathered during December 2018 and January 2019. An initial Web-based search was conducted to retrieve the electronic addresses of all Canadian publicly funded drug plan online formularies, including provincial, territorial, and federal plans. The respective online formularies of the following jurisdictions were searched: British Columbia, Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia, New Brunswick, Prince Edward Island, Newfoundland and Labrador, Yukon, Northwest Territories, Nunavut, Canadian Armed Forces (CAF), Veterans Affairs Canada (VAC), Correctional Services Canada (CSC), and Non-Insured Health Benefits (NIHB) (Table 2).
Table 2: Canadian Publicly Funded Drug Plans
The drugs of interest listed in Table 1 were searched in each jurisdictional drug formulary to obtain their respective listing statuses. Listing statuses of FB, LU, EU, and NB were assigned to each medication of interest for each jurisdiction. For the purpose of this report, FB refers to a medication reimbursed without any criteria; LU refers to a medication reimbursed with criteria but without the need for the review of an application; EU refers to a medication that requires the review of an application; and NB refers to a medication not reimbursed by the jurisdiction. Criteria for LU medications were retrieved, along with criteria for EU drug status, when available in the public domain.
Findings
Reimbursement information for all drugs listed in Table 1 was retrieved from all publicly funded drug plan formularies (Table 2). The listing statuses are summarized in Table 3. Overall, single-drug products of DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists are commonly reimbursed by jurisdictions; however, their listing statuses vary from FB to LU or EU. In contrast, many FDC products, with biguanides or other drugs, are NB drugs. Of note, Ontario is the only province that grants FB status to some medications, including single-drug and FDC products.6 Additionally, the extended health benefits programs in both the Northwest Territories and Nunavut use the NIHB formulary;7-9 this is reflected in the tables beginning on the next page.
DPP-4 inhibitors are generally listed by most jurisdictions, with the exception of alogliptin (Nesina), which is only reimbursed by Quebec.10 SGLT-2 inhibitors are also listed by most jurisdictions; the exception is ertugliflozin, which is not listed by any jurisdiction. This may reflect the fact that, when this Environmental Scan was being prepared, ertugliflozin was being reviewed by CADTH CDR. GLP-1 agonists are not listed by any jurisdiction other than Quebec, which only lists dulaglutide and liraglutide as LU medications.10 The DPP-4 inhibitors/biguanide FDC products follow a similar pattern as the single DPP-4 inhibitor products; the exception is CSC, which does not reimburse any such FDC products.10,11 Most of the SGLT-2 inhibitors/biguanide FDC products are not reimbursed by jurisdictional drug programs. The one exception, dapagliflozin/metformin (Xigduo), is listed by most jurisdictions. In addition, empagliflozin/metformin (Synjardy) is listed by Ontario and Quebec.6,10 No jurisdictions list SGLT-2 inhibitor/DPP-4 inhibitor FDC products or GLP-1 agonists/insulin analogue FDC products.
Table 3: Listing Statuses of the Drugs of Interest
| Drug | BC | AB | SK | MB | ON | QC | NS | NBr | PEI | NL | YK | NWT | NU | CAF | VAC | CSC | NIHB |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DPP-4 Inhibitors | |||||||||||||||||
| Alogliptin/ Nesina | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Linagliptin/ Trajenta | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | LU | LU |
| Saxagliptin/ Onglyza | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Sitagliptin/ Januvia | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| SGLT-2 Inhibitors | |||||||||||||||||
| Canagliflozin/ Invokana | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | LU | LU |
| Dapagliflozin/ Forxiga | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | NB | NB | LU |
| Empagliflozin/ Jardiance | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Ertugliflozin/ Steglatro | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| GLP-1 Agonists | |||||||||||||||||
| Dulaglutide/ Trulicity | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Exenatide/ exenatide XR/Byetta/ Bydureon | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Liraglutide/ Victoza | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Lixisenatide/ Adlyxine | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Semaglutide/ Ozempic | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| DPP-4 Inhibitors/Biguanides | |||||||||||||||||
| Alogliptin/ metformin/ Kazano | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Linagliptin/ metformin/ Jentadueto | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Saxagliptin/ metformin/ Komboglyze | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Sitagliptin/ metformin/ Janumet, Janumet XR | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| SGLT-2 Inhibitors/ Biguanides | |||||||||||||||||
| Canagliflozin/ metformin/ Inkovamet | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Dapagliflozin/ metformin/ Xigduo | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | NB | NB | LU |
| Empagliflozin/ metformin/ Synjardy | NB | NB | NB | NB | FB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Ertugliflozin/ sitagliptin/ Steglujan | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| SGLT-2 Inhibitors/ DPP-4 Inhibitors | |||||||||||||||||
| Dapagliflozin/ saxagliptin/ Qtern | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Empagliflozin/ linagliptin/ Glyxambi | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Ertugliflozin/ sitagliptin/ Steglujan | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| GLP-1 Agonists/ Insulin | |||||||||||||||||
| Liraglutide /insulin degludec/ Xultophy | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Lixisenatide/ insulin glargine/ Soliqua | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
AB = Alberta; BC = British Colombia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; DPP-4 = dipeptidyl peptidase-4; EU = exceptional use; FB = full benefit; GLP-1 = glucagon-like peptide-1; LU = limited use; MB = Manitoba; NBr = New Brunswick; NB = non-benefit; NIHB = Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; NU = Nunavut; NWT = Northwest Territories; ON = Ontario; PEI = Prince Edward Island; QC = Quebec; SGLT-2 = sodium-glucose cotransporter-2; SK = Saskatchewan; VAC = Veteran Affairs Canada; YK = Yukon.
The sections that follow provide more detailed descriptions of the reimbursement statuses of DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists, as presented in Table 3. Further detailed information with regards to medications that were classified as LU or EU is also discussed in the section that follows. The reimbursement statuses of individual drugs and their respective clinical criteria are described in the product-specific tables in Appendix 1.
Dipeptidyl Peptidase-4 Inhibitors
Table 4 summarizes the listing statuses of DPP-4 inhibitors (alogliptin, linagliptin, saxagliptin, and sitagliptin). With respect to reimbursement criteria, the Quebec criteria for alogliptin (Nesina) states that it is used as monotherapy in T2D when metformin or a sulfonylurea is contraindicated or not tolerated.10 Additionally, it can be used in combination with metformin or a sulfonylurea when one of these is contraindicated, not tolerated, or ineffective (i.e., when the glycated hemoglobin [A1C] goal is not achieved). This is different from the criteria outlined for other DPP-4 inhibitors listed in the Quebec formulary; the criteria specify that these can only be used in combination with metformin when a sulfonylurea is contraindicated, not tolerated, or ineffective.10
Table 4: Listing Statuses of the Dipeptidyl Peptidase-4 Inhibitors
| Drug | BC | AB | SK | MB | ON | QC | NS | NBr | PEI | NL | YK | NWT | NU | CAF | VAC | CSC | NIHB |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DPP-4 Inhibitors | |||||||||||||||||
| Alogliptin/ Nesina | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Linagliptin/ Trajenta | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | LU | LU |
| Saxagliptin/ Onglyza | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Sitagliptin/ Januvia | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
AB = Alberta; BC = British Colombia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; DPP-4 = dipeptidyl peptidase-4; EU = exceptional use; FB = full benefit; LU = limited use; MB = Manitoba; NBr = New Brunswick; NB = non-benefit; NIHB = Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; NU = Nunavut; NWT = Northwest Territories; ON = Ontario; PEI = Prince Edward Island; QC = Quebec; SK = Saskatchewan; VAC = Veteran Affairs Canada; YK = Yukon.
For linagliptin (Trajenta), the criteria in all listing jurisdictions indicate that it can be considered as adjunctive therapy to metformin when used with a sulfonylurea or as a replacement for either metformin or a sulfonylurea. Furthermore, the criteria in all jurisdictions except NIHB specify that insulin must not be an option.9
Saxagliptin (Onglyza) has the same criteria and listing statuses as linagliptin with one difference: CSC does not list saxagliptin.11
The criteria for sitagliptin (Januvia) are almost the same as those for linagliptin and saxagliptin; however, the Saskatchewan criteria specify that only patients with T2D with reduced renal function can obtain reimbursement for sitagliptin, as opposed to any patients with T2D.12 British Columbia and CSC do not list sitagliptin.11,13
Overall, DPP-4 inhibitors can be considered as adjunctive therapy following the use of metformin and sulfonylureas or as replacement therapy for either metformin or sulfonylureas.
Sodium-Glucose Cotransporter-2 Inhibitors
Table 5 summarizes the listing statuses of SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin).
Table 5: Listing Statuses of the Sodium-Glucose Cotransporter-2 Inhibitors
| Drug | BC | AB | SK | MB | ON | QC | NS | NB | PEI | NL | YK | NWT | NU | CAF | VAC | CSC | NIHB |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SGLT-2 Inhibitors | |||||||||||||||||
| Canagliflozin/ Invokana | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | LU | LU |
| Dapagliflozin/ Forxiga | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | NB | NB | LU |
| Empagliflozin/ Jardiance | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Ertugliflozin/ Steglatro | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
AB = Alberta; BC = British Colombia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; EU = exceptional use; FB = full benefit; LU = limited use; MB = Manitoba; NBr = New Brunswick; NB = non-benefit; NIHB = Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; NU = Nunavut; NWT = Northwest Territories; ON = Ontario; PEI = Prince Edward Island; QC = Quebec; SGLT-2 = sodium-glucose cotransporter-2; SK = Saskatchewan; VAC = Veteran Affairs Canada; YK = Yukon.
Overall, the criteria for canagliflozin (Invokana) are similar to those for DPP-4 inhibitors; i.e., canagliflozin can be considered adjunctive therapy to metformin used with a sulfonylurea or as a replacement for metformin or sulfonylureas. Of note, the Saskatchewan criteria specify that SGLT-2 inhibitors should not be used in combination with DPP-4 inhibitors.12
Dapagliflozin (Forxiga) is different in terms of which reimbursement criteria will consider its use after initial drug therapy with either metformin or a sulfonylurea. The Alberta criteria for dapagliflozin differ from the criteria for canagliflozin in their definition of first- and second-line therapy; they include both metformin and sulfonylureas, as opposed to metformin as first-line therapy followed by sulfonylureas as second-line therapy.13 The Manitoba, Nova Scotia, New Brunswick, and Yukon criteria for dapagliflozin also differ from canagliflozin to reflect the use of metformin or sulfonylurea as initial drug therapy, similar to Alberta. However Manitoba, Nova Scotia, New Brunswick, and Yukon further suggest that dapagliflozin can be considered after first-line therapy, whereas Alberta suggests dapagliflozin after second-line therapy.14-17 The Quebec criteria for dapagliflozin are different from those for canagliflozin in that the latter can be used as monotherapy without metformin or sulfonylureas while dapagliflozin should be used in association with one or the other.10 The CAF criteria are more detailed than those of other jurisdictions, allowing the patient to add dapagliflozin to insulin without metformin or sulfonylureas.18 The Prince Edward Island and NIHB criteria require the use of metformin and sulfonylureas before dapagliflozin.9,19
The criteria for empagliflozin (Jardiance) are similar to those for canagliflozin where jurisdictions specify that it should be used after metformin and a sulfonylurea. However, Quebec and CAF have included CV risk factors in their criteria.10,18 Empagliflozin is covered in Quebec for patients with antecedents of coronary artery disease (CAD) or peripheral artery disease (PAD) and whose A1C is greater than or equal to 7%.10 The initial request requires the physician to specify the type of CAD or PAD from which the person is suffering. In the CAF criteria, empagliflozin can be considered immediately after metformin if the patients have established CV disease, as defined in the EMPA-REG OUTCOME trial.18
Overall, the drugs pertaining to SGLT-2 inhibitors are regarded differently from each other, whereas canagliflozin can be used after metformin and a sulfonylurea; dapagliflozin can be used after initial therapy of either metformin or a sulfonylurea; and empagliflozin can be used after metformin and a sulfonylurea or after initial therapy of either metformin or a sulfonylurea in Quebec and CAF when the patient has CV risk factors.10,18
Glucagon-Like Peptide-1 Agonists
Table 6 summarizes the listing statuses of all the GLP-1 agonists (dulaglutide, exenatide, liraglutide, lixisenatide, and semaglutide). It shows that only dulaglutide (Trulicity) and liraglutide (Victoza) are reimbursed and only by the province of Quebec.10 The criteria for both drugs are the same except for the outlined maximum daily dose.
Table 6: Listing Statuses of the Glucagon-Like Peptide-1 Agonists
| Drug | BC | AB | SK | MB | ON | QC | NS | NBr | PEI | NL | YK | NWT | NU | CAF | VAC | CSC | NIHB |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| GLP-1 Agonists | |||||||||||||||||
| Dulaglutide/ Trulicity | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Exenatide/ Exenatide XR/ Byetta/Bydureon | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Liraglutide/ Victoza | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Lixisenatide/ Adlyxine | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Semaglutide/ Ozempic | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
AB = Alberta; BC = British Colombia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; GLP-1 = glucagon-like peptide-1; LU = limited use; MB = Manitoba; NB = non-benefit; NBr = New Brunswick; NIHB = Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; NU = Nunavut; NWT = Northwest Territories; ON = Ontario; PEI = Prince Edward Island; QC = Quebec; SK = Saskatchewan; VAC = Veteran Affairs Canada; YK = Yukon.
The criteria for both dulaglutide and liraglutide indicate that the patient must use either drug with metformin concomitantly for uncontrolled T2D and have a body mass index of more than 30 kg/m2 where a DPP-4 inhibitor is contraindicated, not tolerated, or ineffective. Additionally, both medications are only authorized to a maximum of 12 months. To continue the treatment after the first year, the physician must demonstrate that patients have a beneficial effect, defined as a reduction in A1C of at least 0.5% or by the attainment of a target value of 7% or less.
In summary, GLP-1 agonists are generally not reimbursed by Canadian publicly funded drug plans, with the exception of dulaglutide and liraglutide, which are used as alternatives to DPP-4 inhibitors in Quebec.10
Dipeptidyl Peptidase-4 Inhibitors/Biguanides
Table 7 summarizes the listing statuses for DPP-4 inhibitor/biguanide (alogliptin/metformin, linagliptin/metformin, saxagliptin/metformin, and sitagliptin/metformin) FDC products. Statuses for the latter drugs mirror those of the individual DPP-4 inhibitors. The exception is CSC, which does not cover any DPP-4/biguanide FDC products.11
Table 7: Listing Statuses of the Dipeptidyl Peptidase-4 Inhibitors/Biguanides
| Drug | BC | AB | SK | MB | ON | QC | NS | NBr | PEI | NL | YK | NWT | NU | CAF | VAC | CSC | NIHB |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| DPP-4 Inhibitors/Biguanides | |||||||||||||||||
| Alogliptin/metformin/ Kazano | NB | NB | NB | NB | NB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Linagliptin/metformin/ Jentadueto | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Saxagliptin/ metformin | EU | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
| Sitagliptin/metformin/ Janumet, Janumet XR | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | EU | NB | LU |
AB = Alberta; BC = British Colombia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; DPP-4 = dipeptidyl peptidase-4; EU = exceptional use; FB = full benefit; LU = limited use; MB = Manitoba; NB = non-benefit; NBr = New Brunswick; NIHB = Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; NU = Nunavut; NWT = Northwest Territories; ON = Ontario; PEI = Prince Edward Island; QC = Quebec; SK = Saskatchewan; VAC = Veteran Affairs Canada; YK = Yukon.
Although only Quebec reimburses the alogliptin/metformin (Kazano) combination, the criteria differ from those for alogliptin used as a single drug in that the FDC product is used when sulfonylureas are contraindicated, not tolerated, or ineffective, as opposed to being used as an add-on to sulfonylureas.10 Additionally, the optimal maximum dose of metformin must be stable for at least one month before switching to the alogliptin/metformin FDC product.
For the FDC product linagliptin/metformin (Jentadueto), the criteria for most jurisdictions state that it can replace the individual components of linagliptin and metformin in situations when linagliptin coverage has been approved and the patient is stable on metformin. British Columbia, Alberta, Quebec, CSC, and NIHB have the same wording for these criteria as for single linagliptin products.9-11,13,20
Similarly, both saxagliptin/metformin (Komboglyze) and sitagliptin/metformin (Janumet, Janumet XR) have exactly the same criteria as for linagliptin/metformin, where coverage for saxagliptin and sitagliptin has been approved by the jurisdictional drug plan. Of note, the CAF criteria for sitagliptin/metformin do not require the patient to be intolerant to insulin.18
Overall, the criteria for DPP-4 inhibitors/biguanides mirror those for single DPP-4 inhibitor products; i.e., the criteria stipulate that they should be used as adjunctive therapy to dual use of metformin and a sulfonylurea or as a replacement for metformin or a sulfonylurea, with the convenience of having two drugs combined.
Sodium-Glucose Cotransporter-2 Inhibitors/Biguanides
Contrary to the DPP-4 inhibitors/biguanide FDC products, Table 8 shows that reimbursement of the SGLT-2 inhibitor/biguanide FDC products (canagliflozin/metformin, dapagliflozin/metformin, empagliflozin/metformin, and ertugliflozin/metformin) is more restricted than for single SGLT-2 inhibitor products.
Table 8: Listing Statuses of the Sodium-Glucose Cotransporter-2 Inhibitors/Biguanides
| Drug | BC | AB | SK | MB | ON | QC | NS | NBr | PEI | NL | YK | NWT | NU | CAF | VAC | CSC | NIHB |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| SGLT-2 Inhibitors/Biguanides | |||||||||||||||||
| Canagliflozin/ metformin/ Inkovamet. Invokamet XR* | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Dapagliflozin/ metformin/ Xigduo | NB | EU | EU | EU | FB | LU | EU | EU | EU | NB | EU | LU | LU | LU | NB | NB | LU |
| Empagliflozin/ metformin/ Synjardy | NB | NB | NB | NB | FB | LU | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
| Ertugliflozin/ Sitagliptin/ Steglujan | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB | NB |
AB = Alberta; BC = British Colombia; CAF = Canadian Armed Forces; CSC = Correctional Services Canada; EU = exceptional use; LU = limited use; MB = Manitoba; NB = non-benefit; NBr = New Brunswick; NIHB = Non-Insured Health Benefits; NL = Newfoundland and Labrador; NS = Nova Scotia; NU = Nunavut; NWT = Northwest Territories; ON = Ontario; PEI = Prince Edward Island; QC = Quebec; SGLT-2 = sodium-glucose cotransporter-2; SK = Saskatchewan; VAC = Veteran Affairs Canada; YK = Yukon.
Dapagliflozin/metformin (Xigduo) is the FDC product that is most often reimbursed by jurisdictions; the reimbursement criteria for this FDC product mirror those of dapagliflozin (a single-drug product). Similarly to the DPP-4 inhibitor/biguanides criteria, most jurisdictions state that the dapagliflozin/metformin FDC product is to replace the separate use of dapagliflozin and metformin in situations where dapagliflozin coverage has been approved and the patient is stable on their metformin dose.
Empagliflozin/metformin (Synjardy) is the only other such FDC product reimbursed, specifically by Ontario and Quebec.6,10 The criteria outlined for empagliflozin/metformin by Quebec are the same as those for dapagliflozin/metformin, where the FDC product is used when sulfonylureas are contraindicated, not tolerated, or ineffective.10 Additionally, the optimal maximum dose of metformin must be stable for at least one month before switching to the empagliflozin/metformin FDC product.
Overall, SGLT-2 inhibitor/biguanide FDC products are not commonly reimbursed by jurisdictions. When reimbursed, criteria mostly follow those of single SGLT-2 inhibitor products with the improved convenience of having the two entities combined together in a single product.
Limitations
The results of this Environmental Scan are based on a Web-based search of publicly available information from online formularies of Canadian jurisdictional drug plans. Consequently, information about some reimbursement statuses or criteria may be missing. Furthermore, when the listing statuses of medications could not be retrieved from publicly available information sources, it was assumed that the drugs were not reimbursed by the jurisdictions. Use of this approach may be a limitation of this report, should some drugs be reimbursed following case-by-case review in exceptional circumstances. Additionally, while drug plan formularies are regularly updated, some online formularies may not reflect the most recent formulary revisions.
Conclusion
Reimbursement of DPP-4 inhibitors, SGLT-2 inhibitors, and GLP-1 agonists varies significantly across jurisdictional drug plans in Canada. However, some trends were noted.
Most jurisdictions reimburse single DPP-4 inhibitor and SGLT-2 inhibitor products. However, GLP-1 agonists are not reimbursed by most jurisdictions, with the exception of Quebec. Ontario is the only province that fully reimburses some DDP-4 inhibitors and SGLT-2 inhibitors, including a few FDC products. Most other jurisdictions list these as LU or EU products.
The clinical criteria for most DPP-4 inhibitors state they can be considered as adjunctive therapy to the dual use of metformin and sulfonylureas or as a replacement for metformin or sulfonylureas when one of these is contraindicated, not tolerated, or ineffective (i.e., when the A1C goal is not achieved) and when insulin is not an option.
There are slightly different criteria for SGLT-2 inhibitors; some can be used in patients who require treatment optimization after initial therapy with metformin or a sulfonylurea. For empagliflozin specifically, some clinical criteria include CV risk factors.
Apart from Quebec, which reimburses two GLP-1 agonists, these drugs are not currently covered by Canadian drug plans. In Quebec, only dulaglutide and liraglutide are listed, and their status is LU in situations where DPP-4 inhibitors are contraindicated, not tolerated, or ineffective.10 Additionally, the patient must be using metformin and meet a pre-defined body mass index requirement.
With regards to the FDC products, the reimbursement criteria for DPP-4 inhibitor/biguanide FDC products are similar to those for single DPP-4 inhibitor products. Overall, DPP-4 inhibitor/biguanide FDC products are used as add-on therapies to metformin and a sulfonylurea or as a replacement for metformin or a sulfonylurea, with the improved convenience of having these two drugs together in a single product.
Reimbursement of SGLT-2 inhibitor/biguanide FDC products is quite limited; most jurisdictions only list dapagliflozin/metformin (Xigduo). However, empagliflozin/metformin (Synjardy) is also listed by Ontario (FB) and Quebec (LU). Reimbursement criteria for these FDC products generally follow those for single SGLT-2 inhibitor products, with the improved convenience of having both drugs combined in a single product.
FDC products not containing metformin as one of their components — i.e., SGLT-2 Inhibitor/DPP-4 inhibitor combinations and GLP-1 agonists/insulin analogue combinations — are not currently reimbursed by any jurisdictional drug plans in Canada.
Appendices
References
- Health Canada. Type 2 diabetes. Health. Diseases and Conditions 2018; https://www.canada.ca/en/public-health/services/diseases/type-2-diabetes.html. Accessed 2019 Jan 10.
- Diabetes Canada. Diabetes statistics in Canada. https://www.diabetes.ca/how-you-can-help/advocate/why-federal-leadership-is-essential/diabetes-statistics-in-canada. Accessed 2019 Jan 10.
- Berry J. Statistics and facts about type 2 diabetes. Medical News Today 2018; https://www.medicalnewstoday.com/articles/318472.php. Accessed 2019 Jan 09.
- Dibetes Canada. 2018 clinical practice guidelines: CPG quick reference guide. Toronto (ON)2018: http://guidelines.diabetes.ca/docs/CPG-quick-reference-guide-web-EN.pdf. Accessed 2019 Jan 09.
- New drugs for type 2 diabetes: second-line therapy - recommendations report. (CADTH Therapeutic review vol. 4, no. 1c). Ottawa (ON): CADTH; 2017: https://www.cadth.ca/dv/new-drugs-type-2-diabetes-second-line-therapy-recommendations-report. Accessed 2019 Jan 09.
- Ontario Drug Benefit Formulary/Comparative Drug Index. Formulary search. 2018; https://www.formulary.health.gov.on.ca/formulary/. Accessed 2019 Jan 09.
- Health and Social Services Northwest Territories. Supplementary health benefits. https://www.hss.gov.nt.ca/en/services/supplementary-health-benefits. Accessed 2019 Jan 09.
- Department of Health Nunavut. EHB full coverage plan. https://gov.nu.ca/health/information/ehb-full-coverage-plan. Accessed 2019 Jan 09.
- Department of Indigenous Services Canada. Non-insured health benefits - drug benefit list summer 2018. Ottawa (ON): Government of Canada; 2018: https://www.canada.ca/en/indigenous-services-canada/services/non-insured-health-benefits-first-nations-inuit/benefits-services-under-non-insured-health-benefits-program/drugs-pharmacy-benefits/drug-benefit-list.html. Accessed 2019 Jan 09.
- Service des relations avec la clientèle. List of medications. Quebec City (QC): Régie de l'assurance maladie du Quebec; 2018: http://www.ramq.gouv.qc.ca/SiteCollectionDocuments/liste_med/Liste_med_2018_11_15_en.pdf. Accessed 2019 Jan 09.
- Clinical Services Branch Health Services Sector. CSC national formulary. Ottawa (ON): Correctional Service Canada; 2016: https://buyandsell.gc.ca/cds/public/2016/11/03/f945c6b503634dd3c47dd4f50753855a/csc_formulary_apr_2016_en.pdf. Accessed 2019 Jan 09.
- Saskatchewan Ministry of Health. Saskatchewan online formulary database. Saskatchewan drug plan 2018; http://formulary.drugplan.ehealthsask.ca/SearchFormulary. Accessed 2019 Jan 09.
- BC PharmaCare. Formulary search. 2019; https://pharmacareformularysearch.gov.bc.ca/. Accessed 2019 Jan 09.
- Manitoba Health. Manitoba pharmacare program: drug formulary lookup. Provincial drug programs 2019; https://web22.gov.mb.ca/eFormulary/. Accessed 2019 Jan 09.
- Nova Scotia Department of Health. Formulary. Nova Scotia Pharmacare. Halifax (NS): Province of Nova Scotia; 2019: https://novascotia.ca/dhw/pharmacare/documents/formulary.pdf. Accessed 2019 Jan 09.
- New Brunswick Drug Plans. Formulary. Fredricton (NB): Government of New Brunswick; 2019: https://www2.gnb.ca/content/dam/gnb/Departments/h-s/pdf/en/NBDrugPlan/NewBrunswickDrugPlansFormulary.pdf.
- Yukon Drugs Program. Yukon drug formulary. 2019; http://apps.gov.yk.ca/drugs/f?p=161:9000:138766907631317. Accessed 2019 Jan 09.
- National Defence and the Canadian Armed Forces. Canadian Armed Forces drug benefit list. 2018; http://www.cmp-cpm.forces.gc.ca/hs/en/drug-benefit-list/index.asp. Accessed 2019 Jan 09.
- Health PEI. P.E.I. pharmacare formulary. Charlottetown (PE): Province of Prince Edward Island; 2018: https://www.princeedwardisland.ca/sites/default/files/publications/pei_pharmacare_formulary.pdf.
- Albert Health. Interactive drug benefit list. 2019; https://idbl.ab.bluecross.ca/idbl/load.do. Accessed 2019 Jan 09.
About this document
Authors: Vincent Nguyen, Michel Boucher
Ackowledgements: The authors would like to acknowledge the contribution of CADTH Information Specialist Danielle MacDougall for ensuring the quality of the citations used in the references section.
Cite As: Reimbursement of Newer Drugs for Type 2 Diabetes in Canada: An Environmental Scan. Ottawa: CADTH; 2019. (Environmental scan; no. 84).
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