Tonight, I was asked to participate in a debate about whether GLP1 receptor agonists (GLP1RA) or SGLT2 inhibitors (SGLT2i) are the best choice of medication in type 2 diabetes. I was asked to take the side of GLP1RAs.

 

I must admit that I struggled with taking any side in this discussion (though it was fun to try!). Why? Because both classes of medications provide excellent benefits, beyond ‘just’ improving diabetes control (blood sugars).  As blogged previously, both classes are strongly recommended for consideration in the 2020 Diabetes Canada Clinical Practice Guidelines.

 

Please note that for the discussion below, I am speaking about the medication classes generally, and not teasing out the data between medications within each class (please see prior blogs on data regarding specific medications, which you can search in my search box at the top right of this blog).

 

For GLP1RAs [most commonly used in Canada are dulaglutide (Trulicity), liraglutide (Victoza), semaglutide (Ozempic or Rybelsus)], benefits include: 

  • reduced risk of cardiovascular (CV) events (eg heart attack, stroke) in people with existing CV disease, and those at high risk
  • weight loss
  • reduction or prevention of protein loss in the urine (albuminuria) – ie kidney protection
  • greatest improvement in blood sugars, without causing low blood sugars

 

Some GLP1RAs can be so effective for weight loss, that they are now used for weight management in people without type 2 diabetes.  As blogged previously, in our 2020 Canadian Obesity guidelines, we recommend obesity medication for people with a BMI of ≥30 or ≥27 with adiposity-related health issues, with one of the choices being liraglutide 3mg (a GLP1 receptor agonist, trade name Saxenda).  In the United States, semaglutide was just approved for weight management at a higher dose than the diabetes treatment dose, for weight management (trade name Wegovy) – not yet approved in Canada.

 

For SGLT2i’s [in Canada, canagliflozin (Invokana), dapagliflozin (Forxiga), empagliflozin (Jardiance)], benefits include:

  • reduced risk of cardiovascular events (eg heart attack, stroke) in people with existing CV disease
  • prevention of heart failure
  • treatment of heart failure (with reduced ejection fraction)
  • prevention of kidney failure and preservation of kidney function
  • weight loss and blood pressure reduction
  • improvement in blood sugars (more so with better kidney function), without causing low blood sugars

 

The SGLT2i’s are powerful treatments of heart failure, in people with and without type 2 diabetes.  As such, the recently published  2021 Canadian Heart Failure Guidelines have defined a new standard of care for people with heart failure with reduced ejection fraction (HFrEF) that incorporates 4 key medication classes as standard therapy for most patients: an angiotensin receptor-neprilysin inhibitor (ARNI) or ACEI/ARB, a beta blocker, a mineralocorticoid receptor antagonist, and an SGLT2 inhibitor.

Regarding the power of SGLT2i’s for kidney protection, 2020 KDIGO International Guidelines for diabetes management in chronic kidney disease recommend metformin and SGLT2 inhibitors as first line treatments for people with type 2 diabetes and chronic kidney disease.  As blogged previously, there is also strong evidence that SGLT2i has similar capacity to protect the kidneys in people with chronic kidney disease without type 2 diabetes.

 

The beautiful conclusion of this discussion is that both classes of medications have important health benefits.  And, great news – these classes of medications work very well together!  So at the end of the day, it’s not a battle between these two classes.  For many people with type 2 diabetes, both classes of medications should be used.

 

BOTTOM LINE: Both the SGLT2 inhibitors and the GLP1 receptor agonists have benefits beyond blood sugar control.  These medications work in different ways to provide health benefits, and they work very well together.  Both classes should be considered as important vascular risk reduction strategies. 

 

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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