Hot off the presses, the 2024 update to the Diabetes Canada pharmacotherapy chapter was published in congruence with World Diabetes Day. This guideline updates the previous version from 2020.
This guideline offers Canadian health care professionals guidance on how and when to use medications to lower blood sugar, from pills to injectable medications including insulins. The guideline includes an update of studies published up until February 2023.
I’m not covering every element of this chapter today; rather, I’m pulling out some key points that I want to highlight and/or comment on. As the diabetes field is moving at an extraordinary pace these days, I have commented also on some important data that has come out since the end of the guidelines literature search.
Metformin is still recommended as the first line of treatment for most people with type 2 diabetes. Reasons include its efficacy to lower blood sugars, a good long track record of safety, it doesn’t cause low sugars nor weight gain, and it’s cheap. Authors comment that no study has shown that newer medications like GLP1s [(like semaglutide (Ozempic), trulicity (Dulaglutide), liraglutide (Victoza)] , GIP/GLP1 receptor agonist [tirzepatide (Mounjaro)] or SGLT2 inhibitors [ like dapagliflozin (Forxiga), empagliflozin (Jardiance), canagliflozin (Invokana)] have shown better glucose lowering than metformin as a first line treatment – but to be fair, studies haven’t actually compared these newer agents to metformin, as metformin has been considered a background therapy (ie many/most people in these studies were already on metformin). The American and European guidelines have de-emphasized metformin as first line treatment, in appreciation of the multifaceted benefits that other medications (such as GLP1 receptor agonists, GIP/GLP1 receptor agonist, and SGLT2 inhibitors) can provide, including heart/kidney protection and weight loss. These new Canadian guidelines and accompanying User’s Guide do emphasize partnering with each patient and taking that person’s values and goals as an important input to treatment decisions – which may in many cases end up bypassing metformin as first line, in favor of treatments providing multifaceted benefits.
If sugars are so high that the person has symptoms of severely high sugars (dehydration, urinating a lot, blurry vision), or if blood work shows metabolic decompensation, insulin should be started right away (no changes here).
For people at high cardiovascular risk or with cardiovascular disease, with heart failure, or chronic kidney disease, medications that show protection/benefit for these conditions should be used (GLP1 receptor agonists and/or SGLT2 inhibitors), even if blood sugars (A1c) is at target. (Note – in the text discussion, the GLP1RAs listed for cardiovascular risk reduction are dulaglutide (Trulicity), liraglutide (Victoza), and semaglutide (Ozempic) as these medications have shown benefit. Recently, oral semaglutide (Rybelsus) topline results in the SOUL study also demonstrate a 14% reduction in cardiovascular events – data not yet published (disclosure – I was an investigator in this trial).
While we are advised to choose additional blood sugar lowering agents based on clinical priorities including weight loss, weight loss is not featured as a key priority of type 2 diabetes management. This differs from the American and European guidelines which prioritize weight management alongside blood sugar control and cardiorenal (heart/kidney) protection. Because 90% of people with type 2 diabetes have overweight or obesity, because weight loss is part of an holistic treatment approach that provides numerous health benefits, and because most patients with type 2 diabetes and elevated weight describe weight loss as an important priority to them, I am disappointed that Canadian guidelines have not followed suit on this.
The algorithm for how to choose medication is very much simplified from the 2020 version , which is great! Busy clinicians need easy to follow flow charts, and this really nails it. Again, I would have liked to see weight loss (for people with elevated weight) sharing priority with blood sugar control and heart/kidney protection on this figure .
There is a great table that advises on maximum doses of glucose lowering medication by kidney function (as many medications need to be dose reduced, or cannot be used, at lower levels of kidney function).
If you’re wondering why the new class of GIP/GLP1 receptor agonists (tirzepatide/Mounjaro) isn’t included in the flow chart, that’s because it is not yet known whether it reduces cardiovascular risk (the SURPASS CVOT trial is ongoing) nor whether it protects against reduction in kidney function or kidney failure. Tirzepatide has been shown to improve heart failure in people with obesity, almost half of whom had type 2 diabetes, and with similar benefit with or without diabetes – that paper was just published a couple of weeks ago, so couldn’t be included in these guidelines. On that note, semaglutide at weight management dosing of 2.4mg weekly (Wegovy) has shown to improve heart failure symptoms in people with type 2 diabetes, but this is a higher dose than semaglutide for diabetes (Ozempic – 0.5mg, 1mg, or 2mg weekly).
If you’ve heard of the new once weekly insulin icodec (Awiqli) – it’s also not in the guideline as it was approved after the literature search was completed for this chapter. However, it is mentioned in the User’s Guide that accompanies the guideline (along with addressing many clinical questions that require some interpretation of the guideline).
BOTTOM LINE: Our new Diabetes Canada pharmacotherapy guidelines provide an update based on the literature up until February 2023. The guidelines are simplified, easier to read, digest and understand, which is fantastic for busy clinicians! I would have liked to see weight management take a priority alongside heart/kidney protection and glucose control as weight management (in people with type 2 diabetes and elevated weight) is part of an holistic treatment approach, can provide numerous additional health benefits, improve quality of life, and is reported as an important treatment goal in the eyes of most people living with type 2 diabetes and elevated weight.
Disclaimer: I am/have been an investigator in clinical trials of semaglutide, tirzepatide, liraglutide, dulaglutide, dapagliflozin, and empagliflozin. I receive honoraria as a continuing medical education speaker and consultant from the makers of semaglutide, liraglutide and icodec (Novo Nordisk), tirzepatide and dulaglutide (Eli Lilly), empagliflozin (Boehringer Ingelheim/Eli Lilly), and dapagliflozin (Astra Zeneca).
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