Hot off the presses this week are the much anticipated Diabetes Canada Guidelines on medications (pharmacotherapy) for people with type 2 diabetes. The full Diabetes Canada Clinical Practice Guidelines were last published in 2018, and many important clinical trials have been published since then which have significantly changed how we approach treatment of type 2 diabetes.
These updated guidelines incorporate studies published up until October 2019. You’ll see that the algorithm for choice of medications looks quite a bit different from the 2018 version, and here’s why: two classes of medications, namely the GLP1 receptor agonists (GLP1RA) and SGLT2 inhibitors (SGLT2i), have been further proven to have powerful value-added benefits beyond lowering of blood sugars – namely, protection of the heart and kidneys.
With the depth and complexity of clinical trials that need to be considered, the new guidelines may seem a bit daunting at first blush. That being said, here are some of the Key points:
Metformin is still recommended as first line treatment. This is true of most other guidelines around the world. While we don’t know for sure whether metformin protects the heart, we do know that it is effective to improve blood sugars, we have decades of experience with it, it is well tolerated for most people, it doesn’t cause weight gain or low blood sugars, and it’s cheap.
These new guidelines are still ‘glucocentric’, meaning they are structured with attaning target blood sugar control (A1C) as the centerpoint. They recommend adding to metformin with additional medication if glycemic targets are not achieved, or the individual’s clinical status changes (eg should heart disease, kidney disease or heart failure manifest). If your patient has cardiovascular disease, is age over 60 at high risk of cardiovascular disease, or has heart failure or kidney disease, medications from the SGLT2i and GLP1RA classes are recommended based on the clinical trial evidence. If your patient does not meet these criteria but still needs further glucose lowering, then the choice for next medication should be made keeping in mind prevention of cardiovascular events and heart failure, protecting kidneys, weight management goals and of course, avoidance of low blood sugars (again the GLP1RA and SGLT2i dominate as choice agents).
The excellent User’s Guide that accompanies the new Diabetes Canada Guidelines addresses the question of whether medications showing cardiorenal benefits can be prescribed even if A1C is at target and clinical status hasn’t changed. (Note that the recently updated American/European guidelines clearly recommend considering SGLT2i and/or GLP1RA whether or not a person’s diabetes control is already at target with metformin.) The User’s Guide points out that some recent trials have included patients at A1C target, showing benefit for reduction in heart failure and cardiovascular death in people with heart failure (SGLT2i), and reduction in cardiovascular events for people with , or at high risk for, cardiovascular disease (GLP1RA). They also note that the kidney benefits of SGLT2i do not depend on improvements in blood sugar. They suggest that if a person is at A1C target but could benefit from these medications, that switching an existing diabetes medication for one of these meds (rather than adding the medication on top) may be appropriate.
The new algorithm also begs the question – what if a person with newly diagnosed type 2 diabetes already has cardiovascular disease, heart failure or chronic kidney disease? The User’s Guide advises that while there are no outcome trials performed in this setting, it would seem reasonable to start a medication with cardiorenal benefit (again referring to GLP1RA and SGLT2i) at diagnosis of type 2 diabetes.
As to whether we can skip metformin at initial diagnosis of diabetes if a person has pre-existing cardiovascular disease, heart failure, or chronic kidney disease, the User’s Guide advises that this approach ‘may be considered’.
There are also updated recommendations for starting insulin in people with type 2 diabetes, including consideration of the newer basal insulins to reduce risk of low blood sugars. Before adding bolus (mealtime) insulin, it is recommended to consider other medications (GLP1, SGLT2i, or DPP4i) before moving on to add mealtime insulin.
Disclaimer: I receive honoraria as a continuing medical education speaker and consultant from the makers of SGLT2 inhibitors and GLP1 receptor agonists. I have been involved as an investigator in clinical trials of GLP1 receptor agonists and SGLT2 inhibitors.
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