By Barbara Greenwood Dufour

Approximately three million people in Canada are living with diabetes. This includes one in 10 adults, the majority of whom have type 2 diabetes. It’s important that people with type 2 diabetes carefully manage their blood glucose levels because high blood glucose levels (hyperglycemia), when left untreated, can lead to various complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. That’s why people with type 2 diabetes are at a heightened risk for major adverse cardiovascular events (e.g., stroke, heart attack, heart failure) and may have decreased life expectancy.

If people with type 2 diabetes cannot manage their blood glucose levels through diet and exercise, an antihyperglycemia medication may need to be prescribed. Diabetes Canada’s clinical practice guidelines recommend that metformin be the first-line medication used. When metformin is no longer providing adequate blood glucose control, there are several other antihyperglycemia drugs currently available in Canada that can be used instead or added to metformin. These drugs include insulin secretagogues (meglitinides, sulfonylureas), slow- and fast-acting insulin analogues, dipeptidyl peptidase-4 (DPP4) inhibitors, sodium glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, alpha-glucosidase inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists.

Even with all these medication options, some people with type 2 diabetes find it difficult to manage their high blood glucose levels.

A new antidiabetes drug called tirzepatide is currently under development. It combines a GLP-1 receptor agonist with a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. It’s administered once a week by subcutaneous injection, and it would likely be given on its own or along with another antidiabetes medication. It’s thought that, by activating both the GLP-1 and GIP receptors, tirzepatide could be more effective at managing blood glucose and obesity than GLP-1 agonists alone. So, what does the evidence say about this, and what’s the cardiovascular risk associated with this new drug?

To find out, CADTH’s Horizon Scanning Service identified and summarized the available information on tirzepatide for the treatment of hyperglycemia in adults with type 2 diabetes. CADTH is an independent agency that finds, assesses, and summarizes the research on drugs, medical devices, tests, and procedures. Through its Horizon Scanning Service, CADTH gives Canadian health care decision-makers advance notice of emerging health technologies they may need to make decisions about in the near future.

Because tirzepatide is an emerging drug, so far only phase III clinical trials have been completed (phase III clinical trials compare the safety and effectiveness of a new treatment against standard treatment). CADTH reviewed the completed trial results, which show that tirzepatide appears to be effective for reducing hyperglycemia in adults with type 2 diabetes and might be more effective than semaglutide (another GLP-1 receptor agonist) and than insulin degludec and insulin glargine (both long-acting insulin analogues).

Tirzepatide is intended to address cardiovascular risk associated with type 2 diabetes, such as reducing the risk of heart failure with preserved ejection fraction (when the heart pumps normally but isn’t able to relax enough to fill properly). The available studies suggest that tirzepatide doesn’t increase the risk of major adverse cardiovascular events, but the longer-term cardiovascular benefit or risk of tirzepatide is still not known. One study collecting longer-term data on cardiovascular outcomes is underway with results that should be available in 2024. Until this data are available, uptake of tirzepatide to address cardiovascular risk will likely be limited.

In addition to the trials currently in progress focused on people with type 2 diabetes, tirzepatide is also being investigated as a treatment for obesity in people with or without type 2 diabetes.

Tirzepatide has not been approved by Health Canada and is not currently available in Canada. However, the US Food and Drug Administration (FDA) approved tirzepatide just last month (May 13, 2022). CADTH is, therefore, providing Canadian health care decision-makers with useful information and early evidence on tirzepatide to help them prepare for what might be coming up next in diabetes treatment.

CADTH’s report on tirzepatide is freely available on the CADTH website at cadth.ca/tirzepatide-type-2-diabetes-mellitus. To learn more about our Horizon Scanning program, visit cadth.ca/horizon-scanning, or to suggest a new or emerging health technology for CADTH to review, email us at HorizonScanning@cadth.ca. You can also follow us on Twitter @CADTH_ACMTS or speak to a Liaison Officer in your region: cadth.ca/contact-us/liaison-officers.

Barbara Greenwood Dufour is a knowledge mobilization officer at CADTH.